Process Systems Engineering for Pharmaceutical Manufacturing

700 Pages·2018·31.39 MB·English

by  Ravendra Singh

Computer Aided
Chemical Engineering
Process Systems
Engineering for Pharmaceutical
Manufacturing
Volume 41
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Computer Aided
Chemical Engineering
Process Systems
Engineering for Pharmaceutical
Manufacturing
Volume 41
Edited by
Ravendra Singh
Rutgers, The State University of New Jersey,
Piscataway, NJ, United States of America
Zhihong Yuan
Tsinghua University, Beijing, China
Elsevier
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Contents
Contributors............................................................................................................xix
Preface.................................................................................................................xxiii
CHAPTER 1 New Product Development and Supply Chains
in the Pharmaceutical Industry............................................1
CatherineAzzaro-Pantel
1. Introduction.....................................................................................1
2. Typical Features ofPharmaceuticalIndustry.................................2
2.1. Analysis ofthe ProductDevelopmentProcess......................2
2.2. Life Cycle ofa Drug..............................................................3
2.3. Drug Market Features.............................................................5
2.4. Supply ChainManagement....................................................5
3. Management ofProductDevelopmentPipeline............................8
3.1. Methodological Approaches...................................................8
3.2. Related Optimization Works................................................11
4. Capacity Planning.........................................................................18
5. Management ofthe WholePharmaceutical
Supply Chain.................................................................................19
6. Conclusions...................................................................................22
References..........................................................................................23
CHAPTER 2 The development of a pharmaceutical oral
solid dosage forms.................................................................27
Rahamatullah Shaikh,Do´nalP. O’Brien, Denise M. Croker,
Gavin M. Walker
1. Introduction...................................................................................27
2. Pharmaceutical Preformulation and Its Significance inthe
Developmentof Solid Dosage Forms..........................................28
2.1. Solid-StateProperties...........................................................28
2.2. Solubility...............................................................................29
2.3. DissolutionStudies...............................................................32
2.4. Stability Studies....................................................................33
2.5. Drug-Excipient Compatibility Studies.................................34
2.6. Physical Properties of Pharmaceutical Solids......................34
3. Drug Product Manufacturing........................................................35
3.1. Diluents.................................................................................38
3.2. Binders..................................................................................38
v
vi Contents
3.3. DisintegratingAgents...........................................................41
3.4. Lubricant...............................................................................41
3.5. Coating Materials.................................................................42
4. Manufacturing Methods for Oral Solid Dosage Form.................45
4.1. Direct Compression..............................................................46
4.2. Granulation...........................................................................47
5. Type ofUnit Operation................................................................50
5.1. PharmaceuticalProcessDesign Methodology.....................50
5.2. Unit Operation Design..........................................................51
6. Batch Versus Continuous Processing...........................................58
7. Process Analytical Technology....................................................60
8. Conclusions...................................................................................63
References..........................................................................................63
CHAPTER 3 Innovative process development and
production concepts for small-molecule API
manufacturing..........................................................................67
JohnM. Woodley
1. Introduction...................................................................................67
2. PharmaceuticalProductionProcesses..........................................68
2.1. Production ofHigh-Molecular-Weight Pharmaceutical
Products.................................................................................69
2.2. Production ofLow-Molecular-Weight Pharmaceutical
Products.................................................................................69
3. InnovativeSolutions toAccelerate the Development
ofAPI Production Processes........................................................71
3.1. Virtual Experimentation.......................................................71
3.2. Databases and Property Prediction.......................................71
3.3. Template Processes...............................................................72
3.4. Summary...............................................................................74
4. InnovativeSolutions toImprove API Production
Processes.......................................................................................74
4.1. ProcessAnalytical Technology............................................75
4.2. ProcessIntegration andIntensification................................76
4.3. SolventSelection..................................................................77
4.4. Biocatalysis...........................................................................77
4.5. Flow Chemistry....................................................................78
5. Example:Sitagliptin.....................................................................79
6. Future Perspectives.......................................................................80
References..........................................................................................81
Contents vii
CHAPTER 4 Plantwide technoeconomic analysis and
separation solvent selection for continuous
pharmaceutical manufacturing: Ibuprofen,
artemisinin, and diphenhydramine...................................85
Samir A. Diab, Hikaru G.Jolliffe, DimitriosI. Gerogiorgis
1. Introduction...................................................................................86
2. CPM ofIbuprofen, Artemisinin,and Diphenhydramine.............88
2.1. Continuous-FlowSyntheses.................................................88
2.2. Batch and Continuous Separation Schemes.........................90
3. Economic Analysis.......................................................................95
4. Results and Discussion.................................................................99
4.1. API Recoveries andMaterial Efficiencies...........................99
4.2. Economic Analysis.............................................................104
5. Conclusions.................................................................................109
Acknowledgments...........................................................................110
Appendix A. API Recoveriesand PMIs..........................................................110
Appendix B. CapEx, OpEx and SensitivityAnalyses.....................................110
References........................................................................................118
CHAPTER 5 Flowsheet modeling of a continuous direct
compression process...........................................................121
Seongkyu Yoon, Shaun Galbraith, Bumjoon Cha, Huolong Liu
1. Introduction.................................................................................121
1.1. Flowsheet modeling............................................................123
2. Continuous Direct Compression.................................................125
2.1. Powder Feeding..................................................................125
2.2. Methods ofModeling for PowderFeeding........................127
2.3. Powder Blending................................................................129
2.4. ModelingMethodsfor Powder Blending...........................130
2.5. Tablet press.........................................................................133
2.6. Modelingmethods for the TabletPress.............................133
References........................................................................................137
Further Reading...............................................................................139
CHAPTER 6 Applications of a plant-wide dynamic model of
an integrated continuous pharmaceutical plant:
Design of the recycle in the case of multiple
impurities.................................................................................141
Brahim Benyahia
1. Introduction.................................................................................141
2. Process Description.....................................................................142
viii Contents
3. Plant-Wide Model.......................................................................144
4. Results andDiscussions..............................................................146
4.1. Impact of Wash Factors.....................................................149
4.2. Impact of Purge Ratio........................................................151
5. Conclusions.................................................................................155
References........................................................................................156
CHAPTER 7 Advanced multiphase hybrid model development
of fluidized bed wet granulation processes................159
AshutoshTamrakar,Dheeraj R.Devarampally,
Rohit Ramachandran
1. Introduction toGranulation Modeling.......................................159
1.1. Fluid Bed Model Development: Multiphase Flow
and Granulation..................................................................161
1.2. DifferentModeling Techniques.........................................164
2. Multiphase Model Development and Implementation:
FluidizedBed Wet Granulation..................................................169
2.1. CFD-DEM: Model Development.......................................169
2.2. PBM: Compartmental Model Development......................172
2.3. CFD-DEM-PBM:Model Implementation.........................175
3. Results andDiscussion...............................................................177
3.1. CFD-DEMSimulation Results...........................................177
3.2. PBM Results and Validation ofHybrid Model.................182
4. Summary.....................................................................................184
References........................................................................................184
CHAPTER 8 Global sensitivity, feasibility, and flexibility
analysis of continuous pharmaceutical
manufacturing processes...................................................189
Zilong Wang, MarianthiIerapetritou
1. Introduction.................................................................................189
2. Global SensitivityAnalysis........................................................191
2.1. Methods...............................................................................192
2.2. Visualization of SensitivityResults...................................200
3. Feasibility and Flexibility Analysis............................................201
3.1. Methods...............................................................................202
3.2. Visualization of Results......................................................208
3.3. Extensions...........................................................................209
4. Software......................................................................................209
5. Conclusion and Future Perspectives...........................................209
Acknowledgments...........................................................................210
References........................................................................................211
Contents ix
CHAPTER 9 Crystallization process monitoring and control
using process analytical technology.............................215
Levente L. Simon, Elena Simone, Kaoutar Abbou Oucherif
1. Introduction.................................................................................216
2. QbDand PAT.............................................................................216
3. Liquid- and Solid-PhaseMonitoring..........................................218
3.1. ATR-FTIR andUltraviolet-Visible Spectroscopy.............218
3.2. Conductivity Measurements...............................................219
3.3. Refractive Index Measurement..........................................219
3.4. Turbidity Measurement......................................................219
3.5. FBRM.................................................................................220
3.6. PVM and Endoscopy..........................................................220
3.7. Raman Spectroscopy..........................................................221
3.8. Acoustic Spectroscopy(Ultrasound)..................................221
4. Monitoring andControlof Batch CrystallizationProcesses.....221
4.1. Optimal Switching Between Nucleationand
Seed RipeningUsing ControlCharts.................................221
4.2. Concentration FeedbackControl........................................222
4.3. ADNC.................................................................................224
4.4. Polymorphic FeedbackControl..........................................226
4.5. Polymorphic Controlby Optimal SolventSelection.........229
5. Monitoring andControlof Continuous Crystallization
Processes.....................................................................................231
5.1. ADNC of Continuous Crystallization Processes...............231
5.2. Polymorphic ControlinContinuous Crystallization..........234
5.3. Encrustation Monitoring inContinuousCrystallization....235
References........................................................................................237
Further Reading...............................................................................242
CHAPTER 10 BioProcess performance monitoring using
multiway interval partial least squares........................243
Shallon Stubbs, Jie Zhang, Julian Morris
1. Motivation and Background.......................................................243
2. Combiningdata Unfolding andIntervalSplicing Techniques..244
2.1. Three-DimensionalData Unfolding...................................244
2.2. Combining Data Unfoldingand IntervalSplicing.............245
3. Fed-Batch Penicillin Simulator Prediction andFault
Monitoring...................................................................................248
3.1. Fed-Batch Penicillin Production ProcessSimulator
Overview.............................................................................248
3.2. Prediction andProcessMonitoring....................................250