Edited by Dr. Defang Ouyang is Associate Professor, Institute of Chinese Medical Sciences and Faculty of Health Sciences, University of Macau. With more than twenty years of experience in academia and industry, Dr. Ouyang has pioneered the integration of multi-scale modeling, Artificial Intelligence, and Big Data techniques in the field of drug delivery. He developed six approved patents and published two books, several book chapters, and over 100 refereed journal papers.

• List of Contributors xvPreface xxi1 Introduction to Computational Pharmaceutics 1Nannan Wang, Wei Wang, Hao Zhong, and Defang Ouyang1.1 Current Pharmaceutical Research 21.2 What is Computational Pharmaceutics? 51.3 About This Book 72 Opportunities and Challenges of Artificial Intelligence (AI) in Drug Delivery 10Zhuyifan Ye and Defang Ouyang2.1 Introduction 122.2 Machine Learning Algorithms 142.3 Applications of Machine Learning in Pharmaceutics 222.4 Applications of Large-Scale Models in Drug Discovery and Development 402.5 AI in the Clinic and Precision Medicine 442.6 Opportunities and Challenges 452.7 Summary 483 Computational Resources in Pharmaceutics 59Jie Dong3.1 Concept and Overview of Computational Pharmaceutics 603.2 Databases 623.3 Computational Platforms/Web Servers 673.4 Implementation Methods for Databases and Computing Platforms 793.5 Summary and Outlook 814 Computational Modeling of Dry Powder Inhalation 85Jiawei Hu, Ling Zhang, and Chuan-Yu Wu4.1 Introduction 864.2 Discrete Element Methods (DEMs) 874.3 Modeling of Agglomeration 894.4 Modeling of De-agglomeration 914.5 Modeling of Particle Dispersion in DPIs 954.6 Summary and Perspectives 985 Molecular Modeling in Drug Delivery: Polymer Protective Coatings as Case Study 104Alex Bunker and Josef Kehrein5.1 Introduction 1075.2 Molecular Dynamics Simulation of Polymers in Drug Delivery 1255.3 Conclusion 1636 3D Structural Investigation of Solid Dosage Forms 199Xianzhen Yin, Chenxi Huang, Zeying Cao, Li Wu, Tiqiao Xiao, Peter York, and Jiwen Zhang6.1 Structure of Solid Dosage Forms and Methods of Investigation -- An Overview 2006.2 Synchrotron Radiation X-ray Computed Microtomography 2046.3 3D Structure Reconstruction Based on SR-μCT 2056.4 3D Visualization and Quantitative Characterization 2106.5 Future Prospects 2297 Dissolution Mechanism of Pharmaceuticals and Formulations by Nonequilibrium Thermodynamic Modeling 235Yuanhui Ji, Zheng Zhang, Kai Ge, Raphael Paus, and Gabriele Sadowski7.1 Introduction 2367.2 Theoretical Basis and Models 2387.3 Experimental Methods 2447.4 Mechanism Analysis and Model Predictions 2467.5 Conclusions and Outlook 2618 Physiologically Based Pharmacokinetics 267Ruihu Du and Dongyang Liu8.1 Definition and History of Physiologically Based Pharmacokinetics 2688.2 Principles and Structures of the Physiologically Based Pharmacokinetics Model 2698.3 Physiologically Based Pharmacokinetics Model in Complex Situations 2848.4 Challenges and Perspectives of the Physiologically Based Pharmacokinetics Model 2889 Molecular Modeling in Drug Delivery 293Jiawen Wang, Yi Yu, and Youyong Li9.1 Introduction 2949.2 Basic Principles of Molecular Dynamic Simulation and Molecular Modeling Methods 3009.3 Molecular Dynamic Simulation of Drug Delivery Strategies with Nanoparticles 3039.4 Summary 32010 Integration of Dendrimer-Based Delivery Technologies with Computational Pharmaceutics and Their Potential in the Era of Nanomedicine 328Karnaker Reddy Tupally, Prasenjit Seal, Preeti Pandey, Rink-Jan Lohman, Sean Smith, Defang Ouyang, and Haredra Parekh10.1 Introduction 32910.2 Dendrimers as Drug/Gene Delivery Systems and Their Pharmaceutical Applications 33110.3 Computational Aspects of Dendrimer-Based Drug Delivery and Challenges 36310.4 Conclusions 36711 Artificial Intelligence and Computational Modeling in Orally Inhaled Drugs 379Renjie Li, Hao Miao, Xudong Zhou, Ruiping Zou, and Zhenbo Tong11.1 Overview 38111.2 Chronic Respiratory Diseases and Inhaled Therapy 38111.3 Introduction of Computational Methods 38311.4 Applications in R&D of Inhalers and Drug Formulations 38611.5 Applications in the Evaluation of Inhaled Drug Efficacy 38911.6 Applications in the Management of Chronic Respiratory Diseases 39411.7 Challenges and Future 39711.8 Conclusions 39912 Digital Formulation Development Using 3D Printing Technology: AI and Modeling 408Timothy Tracy, Lei Wu, Senping Cheng, and Xiaoling Li12.1 Introduction 40912.2 3D Printing Methods in the Formulation of Pharmaceuticals 41112.3 Novel Tablet Structures Possible with 3D Printing 41512.4 Artificial Intelligence in Formulation Development Using 3D Printing 41612.5 3D Printing Formulation by Design 43012.6 Summary 43213 A Review on Research and Application of Expert Systems on Drug Formulation and Process Design 437Ruofei Du and Yu Zhang13.1 Introduction 43713.2 The Structure of ES 43813.3 Applications 44913.4 Discussions 46614 Application of PBPK Modeling in Formulation Development 474Bo Liu and Xue Li14.1 Introduction 47514.2 Pharmacokinetic (PK) Software for Modeling 47614.3 Modeling Mechanisms for Different Types of Dosage Forms 47914.4 Summary and Conclusion 48915 Multiscale Models for Tablet Manufacturing Process Development 493Xizhong Chen, Kai Liu, LiGe Wang, Liang Li, and Zheng-Hong Luo15.1 Introduction 49415.2 Tablet Manufacturing 49615.3 Computational Modeling 49915.4 Case Studies 50615.5 Summary and Outlook 51316 Machine Learning as a Part of Pharmaceutical Product Development 517Johan Botker, Jukka Rantanen, and Anders O. Madsen16.1 Introduction 51816.2 Pharmaceutical Materials Science 51916.3 Product Design 52416.4 Processing of Pharmaceuticals 52616.5 Analytical Chemistry in a Pharmaceutical Setting 52916.6 Concluding Remarks 53017 Big Data Analysis of Patents and Their Applications in Biomedical Research and Development 533Jiaqi Xu, Jialu Yuan, Hong Cai, and Yuanjia Hu17.1 Introduction 53417.2 Patent Landscape Analysis 53617.3 Mining Chemical Information from Patents 54017.4 Mining Biological Information from Patents 54617.5 Mining Pharmaceutics Information from Patents 55317.6 Practical Operations and Related Issues 55617.7 Outlook 56818 Model-informed Drug Development (MIDD) Regarding Regulatory Requirements and Thinking 574Wei Wang, Yuzhu Wang, and Defang Ouyang18.1 Driving Forces Toward MIDD 57618.2 Regulatory Guidance on Modeling Methods 57818.3 Evolving Thinking on MIDD 58218.4 The Advancement of Pharmacometrics in China 58818.5 Summary 589References 589Index 593

Edited by Dr. Defang Ouyang is Associate Professor, Institute of Chinese Medical Sciences and Faculty of Health Sciences, University of Macau. With more than twenty years of experience in academia and industry, Dr. Ouyang has pioneered the integration of multi-scale modeling, Artificial Intelligence, and Big Data techniques in the field of drug delivery. He developed six approved patents and published two books, several book chapters, and over 100 refereed journal papers.

• List of Contributors xvPreface xxi1 Introduction to Computational Pharmaceutics 1Nannan Wang, Wei Wang, Hao Zhong, and Defang Ouyang1.1 Current Pharmaceutical Research 21.2 What is Computational Pharmaceutics? 51.3 About This Book 72 Opportunities and Challenges of Artificial Intelligence (AI) in Drug Delivery 10Zhuyifan Ye and Defang Ouyang2.1 Introduction 122.2 Machine Learning Algorithms 142.3 Applications of Machine Learning in Pharmaceutics 222.4 Applications of Large-Scale Models in Drug Discovery and Development 402.5 AI in the Clinic and Precision Medicine 442.6 Opportunities and Challenges 452.7 Summary 483 Computational Resources in Pharmaceutics 59Jie Dong3.1 Concept and Overview of Computational Pharmaceutics 603.2 Databases 623.3 Computational Platforms/Web Servers 673.4 Implementation Methods for Databases and Computing Platforms 793.5 Summary and Outlook 814 Computational Modeling of Dry Powder Inhalation 85Jiawei Hu, Ling Zhang, and Chuan-Yu Wu4.1 Introduction 864.2 Discrete Element Methods (DEMs) 874.3 Modeling of Agglomeration 894.4 Modeling of De-agglomeration 914.5 Modeling of Particle Dispersion in DPIs 954.6 Summary and Perspectives 985 Molecular Modeling in Drug Delivery: Polymer Protective Coatings as Case Study 104Alex Bunker and Josef Kehrein5.1 Introduction 1075.2 Molecular Dynamics Simulation of Polymers in Drug Delivery 1255.3 Conclusion 1636 3D Structural Investigation of Solid Dosage Forms 199Xianzhen Yin, Chenxi Huang, Zeying Cao, Li Wu, Tiqiao Xiao, Peter York, and Jiwen Zhang6.1 Structure of Solid Dosage Forms and Methods of Investigation -- An Overview 2006.2 Synchrotron Radiation X-ray Computed Microtomography 2046.3 3D Structure Reconstruction Based on SR-μCT 2056.4 3D Visualization and Quantitative Characterization 2106.5 Future Prospects 2297 Dissolution Mechanism of Pharmaceuticals and Formulations by Nonequilibrium Thermodynamic Modeling 235Yuanhui Ji, Zheng Zhang, Kai Ge, Raphael Paus, and Gabriele Sadowski7.1 Introduction 2367.2 Theoretical Basis and Models 2387.3 Experimental Methods 2447.4 Mechanism Analysis and Model Predictions 2467.5 Conclusions and Outlook 2618 Physiologically Based Pharmacokinetics 267Ruihu Du and Dongyang Liu8.1 Definition and History of Physiologically Based Pharmacokinetics 2688.2 Principles and Structures of the Physiologically Based Pharmacokinetics Model 2698.3 Physiologically Based Pharmacokinetics Model in Complex Situations 2848.4 Challenges and Perspectives of the Physiologically Based Pharmacokinetics Model 2889 Molecular Modeling in Drug Delivery 293Jiawen Wang, Yi Yu, and Youyong Li9.1 Introduction 2949.2 Basic Principles of Molecular Dynamic Simulation and Molecular Modeling Methods 3009.3 Molecular Dynamic Simulation of Drug Delivery Strategies with Nanoparticles 3039.4 Summary 32010 Integration of Dendrimer-Based Delivery Technologies with Computational Pharmaceutics and Their Potential in the Era of Nanomedicine 328Karnaker Reddy Tupally, Prasenjit Seal, Preeti Pandey, Rink-Jan Lohman, Sean Smith, Defang Ouyang, and Haredra Parekh10.1 Introduction 32910.2 Dendrimers as Drug/Gene Delivery Systems and Their Pharmaceutical Applications 33110.3 Computational Aspects of Dendrimer-Based Drug Delivery and Challenges 36310.4 Conclusions 36711 Artificial Intelligence and Computational Modeling in Orally Inhaled Drugs 379Renjie Li, Hao Miao, Xudong Zhou, Ruiping Zou, and Zhenbo Tong11.1 Overview 38111.2 Chronic Respiratory Diseases and Inhaled Therapy 38111.3 Introduction of Computational Methods 38311.4 Applications in R&D of Inhalers and Drug Formulations 38611.5 Applications in the Evaluation of Inhaled Drug Efficacy 38911.6 Applications in the Management of Chronic Respiratory Diseases 39411.7 Challenges and Future 39711.8 Conclusions 39912 Digital Formulation Development Using 3D Printing Technology: AI and Modeling 408Timothy Tracy, Lei Wu, Senping Cheng, and Xiaoling Li12.1 Introduction 40912.2 3D Printing Methods in the Formulation of Pharmaceuticals 41112.3 Novel Tablet Structures Possible with 3D Printing 41512.4 Artificial Intelligence in Formulation Development Using 3D Printing 41612.5 3D Printing Formulation by Design 43012.6 Summary 43213 A Review on Research and Application of Expert Systems on Drug Formulation and Process Design 437Ruofei Du and Yu Zhang13.1 Introduction 43713.2 The Structure of ES 43813.3 Applications 44913.4 Discussions 46614 Application of PBPK Modeling in Formulation Development 474Bo Liu and Xue Li14.1 Introduction 47514.2 Pharmacokinetic (PK) Software for Modeling 47614.3 Modeling Mechanisms for Different Types of Dosage Forms 47914.4 Summary and Conclusion 48915 Multiscale Models for Tablet Manufacturing Process Development 493Xizhong Chen, Kai Liu, LiGe Wang, Liang Li, and Zheng-Hong Luo15.1 Introduction 49415.2 Tablet Manufacturing 49615.3 Computational Modeling 49915.4 Case Studies 50615.5 Summary and Outlook 51316 Machine Learning as a Part of Pharmaceutical Product Development 517Johan Botker, Jukka Rantanen, and Anders O. Madsen16.1 Introduction 51816.2 Pharmaceutical Materials Science 51916.3 Product Design 52416.4 Processing of Pharmaceuticals 52616.5 Analytical Chemistry in a Pharmaceutical Setting 52916.6 Concluding Remarks 53017 Big Data Analysis of Patents and Their Applications in Biomedical Research and Development 533Jiaqi Xu, Jialu Yuan, Hong Cai, and Yuanjia Hu17.1 Introduction 53417.2 Patent Landscape Analysis 53617.3 Mining Chemical Information from Patents 54017.4 Mining Biological Information from Patents 54617.5 Mining Pharmaceutics Information from Patents 55317.6 Practical Operations and Related Issues 55617.7 Outlook 56818 Model-informed Drug Development (MIDD) Regarding Regulatory Requirements and Thinking 574Wei Wang, Yuzhu Wang, and Defang Ouyang18.1 Driving Forces Toward MIDD 57618.2 Regulatory Guidance on Modeling Methods 57818.3 Evolving Thinking on MIDD 58218.4 The Advancement of Pharmacometrics in China 58818.5 Summary 589References 589Index 593

Edited by Dr. Defang Ouyang is Associate Professor, Institute of Chinese Medical Sciences and Faculty of Health Sciences, University of Macau. With more than twenty years of experience in academia and industry, Dr. Ouyang has pioneered the integration of multi-scale modeling, Artificial Intelligence, and Big Data techniques in the field of drug delivery. He developed six approved patents and published two books, several book chapters, and over 100 refereed journal papers.

• List of Contributors xvPreface xxi1 Introduction to Computational Pharmaceutics 1Nannan Wang, Wei Wang, Hao Zhong, and Defang Ouyang1.1 Current Pharmaceutical Research 21.2 What is Computational Pharmaceutics? 51.3 About This Book 72 Opportunities and Challenges of Artificial Intelligence (AI) in Drug Delivery 10Zhuyifan Ye and Defang Ouyang2.1 Introduction 122.2 Machine Learning Algorithms 142.3 Applications of Machine Learning in Pharmaceutics 222.4 Applications of Large-Scale Models in Drug Discovery and Development 402.5 AI in the Clinic and Precision Medicine 442.6 Opportunities and Challenges 452.7 Summary 483 Computational Resources in Pharmaceutics 59Jie Dong3.1 Concept and Overview of Computational Pharmaceutics 603.2 Databases 623.3 Computational Platforms/Web Servers 673.4 Implementation Methods for Databases and Computing Platforms 793.5 Summary and Outlook 814 Computational Modeling of Dry Powder Inhalation 85Jiawei Hu, Ling Zhang, and Chuan-Yu Wu4.1 Introduction 864.2 Discrete Element Methods (DEMs) 874.3 Modeling of Agglomeration 894.4 Modeling of De-agglomeration 914.5 Modeling of Particle Dispersion in DPIs 954.6 Summary and Perspectives 985 Molecular Modeling in Drug Delivery: Polymer Protective Coatings as Case Study 104Alex Bunker and Josef Kehrein5.1 Introduction 1075.2 Molecular Dynamics Simulation of Polymers in Drug Delivery 1255.3 Conclusion 1636 3D Structural Investigation of Solid Dosage Forms 199Xianzhen Yin, Chenxi Huang, Zeying Cao, Li Wu, Tiqiao Xiao, Peter York, and Jiwen Zhang6.1 Structure of Solid Dosage Forms and Methods of Investigation -- An Overview 2006.2 Synchrotron Radiation X-ray Computed Microtomography 2046.3 3D Structure Reconstruction Based on SR-μCT 2056.4 3D Visualization and Quantitative Characterization 2106.5 Future Prospects 2297 Dissolution Mechanism of Pharmaceuticals and Formulations by Nonequilibrium Thermodynamic Modeling 235Yuanhui Ji, Zheng Zhang, Kai Ge, Raphael Paus, and Gabriele Sadowski7.1 Introduction 2367.2 Theoretical Basis and Models 2387.3 Experimental Methods 2447.4 Mechanism Analysis and Model Predictions 2467.5 Conclusions and Outlook 2618 Physiologically Based Pharmacokinetics 267Ruihu Du and Dongyang Liu8.1 Definition and History of Physiologically Based Pharmacokinetics 2688.2 Principles and Structures of the Physiologically Based Pharmacokinetics Model 2698.3 Physiologically Based Pharmacokinetics Model in Complex Situations 2848.4 Challenges and Perspectives of the Physiologically Based Pharmacokinetics Model 2889 Molecular Modeling in Drug Delivery 293Jiawen Wang, Yi Yu, and Youyong Li9.1 Introduction 2949.2 Basic Principles of Molecular Dynamic Simulation and Molecular Modeling Methods 3009.3 Molecular Dynamic Simulation of Drug Delivery Strategies with Nanoparticles 3039.4 Summary 32010 Integration of Dendrimer-Based Delivery Technologies with Computational Pharmaceutics and Their Potential in the Era of Nanomedicine 328Karnaker Reddy Tupally, Prasenjit Seal, Preeti Pandey, Rink-Jan Lohman, Sean Smith, Defang Ouyang, and Haredra Parekh10.1 Introduction 32910.2 Dendrimers as Drug/Gene Delivery Systems and Their Pharmaceutical Applications 33110.3 Computational Aspects of Dendrimer-Based Drug Delivery and Challenges 36310.4 Conclusions 36711 Artificial Intelligence and Computational Modeling in Orally Inhaled Drugs 379Renjie Li, Hao Miao, Xudong Zhou, Ruiping Zou, and Zhenbo Tong11.1 Overview 38111.2 Chronic Respiratory Diseases and Inhaled Therapy 38111.3 Introduction of Computational Methods 38311.4 Applications in R&D of Inhalers and Drug Formulations 38611.5 Applications in the Evaluation of Inhaled Drug Efficacy 38911.6 Applications in the Management of Chronic Respiratory Diseases 39411.7 Challenges and Future 39711.8 Conclusions 39912 Digital Formulation Development Using 3D Printing Technology: AI and Modeling 408Timothy Tracy, Lei Wu, Senping Cheng, and Xiaoling Li12.1 Introduction 40912.2 3D Printing Methods in the Formulation of Pharmaceuticals 41112.3 Novel Tablet Structures Possible with 3D Printing 41512.4 Artificial Intelligence in Formulation Development Using 3D Printing 41612.5 3D Printing Formulation by Design 43012.6 Summary 43213 A Review on Research and Application of Expert Systems on Drug Formulation and Process Design 437Ruofei Du and Yu Zhang13.1 Introduction 43713.2 The Structure of ES 43813.3 Applications 44913.4 Discussions 46614 Application of PBPK Modeling in Formulation Development 474Bo Liu and Xue Li14.1 Introduction 47514.2 Pharmacokinetic (PK) Software for Modeling 47614.3 Modeling Mechanisms for Different Types of Dosage Forms 47914.4 Summary and Conclusion 48915 Multiscale Models for Tablet Manufacturing Process Development 493Xizhong Chen, Kai Liu, LiGe Wang, Liang Li, and Zheng-Hong Luo15.1 Introduction 49415.2 Tablet Manufacturing 49615.3 Computational Modeling 49915.4 Case Studies 50615.5 Summary and Outlook 51316 Machine Learning as a Part of Pharmaceutical Product Development 517Johan Botker, Jukka Rantanen, and Anders O. Madsen16.1 Introduction 51816.2 Pharmaceutical Materials Science 51916.3 Product Design 52416.4 Processing of Pharmaceuticals 52616.5 Analytical Chemistry in a Pharmaceutical Setting 52916.6 Concluding Remarks 53017 Big Data Analysis of Patents and Their Applications in Biomedical Research and Development 533Jiaqi Xu, Jialu Yuan, Hong Cai, and Yuanjia Hu17.1 Introduction 53417.2 Patent Landscape Analysis 53617.3 Mining Chemical Information from Patents 54017.4 Mining Biological Information from Patents 54617.5 Mining Pharmaceutics Information from Patents 55317.6 Practical Operations and Related Issues 55617.7 Outlook 56818 Model-informed Drug Development (MIDD) Regarding Regulatory Requirements and Thinking 574Wei Wang, Yuzhu Wang, and Defang Ouyang18.1 Driving Forces Toward MIDD 57618.2 Regulatory Guidance on Modeling Methods 57818.3 Evolving Thinking on MIDD 58218.4 The Advancement of Pharmacometrics in China 58818.5 Summary 589References 589Index 593