Molecular modeling techniques have been widely used in drug discovery fields for rational drug design and compound screening. Now these techniques are used to model or mimic the behavior of molecules, and help us study formulation at the molecular level. Computational pharmaceutics enables us to understand the mechanism of drug delivery, and to develop new drug delivery systems.
The book discusses the modeling of different drug delivery systems, including cyclodextrins, solid dispersions, polymorphism prediction, dendrimer-based delivery systems, surfactant-based micelle, polymeric drug delivery systems, liposome, protein/peptide formulations, non-viral gene delivery systems, drug-protein binding, silica nanoparticles, carbon nanotube-based drug delivery systems, diamond nanoparticles and layered double hydroxides (LDHs) drug delivery systems.
Although there are a number of existing books about rational drug design with molecular modeling techniques, these techniques still look mysterious and daunting for pharmaceutical scientists. This book fills the gap between pharmaceutics and molecular modeling, and presents a systematic and overall introduction to computational pharmaceutics. It covers all introductory, advanced and specialist levels. It provides a totally different perspective to pharmaceutical scientists, and will greatly facilitate the development of pharmaceutics. It also helps computational chemists to look for the important questions in the drug delivery field.
This book is included in theAdvances in Pharmaceutical Technology book series.
List of Contributors xi
Series Preface xiii
Preface xv
Editors' Biographies xvii
1 Introduction to Computational Pharmaceutics 1
Defang Ouyang and Sean C. Smith
1.1 What Is Computational Pharmaceutics? 1
1.2 Application of Computational Pharmaceutics 3
1.3 Future Prospects 4
2 Crystal Energy Landscapes for Aiding?@Crystal Form Selection 7
Sarah L. Price
2.1 Introduction 7
2.2 CSP Methods for Generating Crystal Energy Landscapes 10
2.3 Examples of the Use of Crystal Energy Landscapes as a Complement to?@Solid Form Screening 18
2.4 Outlook 24
3 Solubilization of Poorly Soluble Drugs: Cyclodextrin?]Based Formulations 31
Sachin S. Thakur, Harendra S. Parekh, Carl H. Schwable, Yong Gan, and Defang Ouyang
3.1 Cyclodextrins in Pharmaceutical Formulations Overview 31
3.2 Drug?]CD Complexes Preparation Methods 35
3.3 Physicochemical Principles Underlying Drug?]CD Complexes 36
3.4 Characterization of Drug?]CD Complexes 38
3.5 Theoretical Progress of CD Studies 41
3.6 Future Prospects of Cyclodextrin Formulation 44
4 Molecular Modeling of Block Copolymer Self?]Assembly and Micellar Drug Delivery 53
Myungshim Kang, Dennis Lam, Dennis E. Discher, and Sharon M. Loverde
4.1 Introduction 53
4.2 Simulation Methods 58
4.3 Simulations of Micellar Drug Delivery 63
4.4 Taxol 68
4.5 Summary and Conclusions 74
5 Solid Dispersiona Pragmatic Method to Improve the Bioavailability of Poorly Soluble Drugs 81
Peng Ke, Sheng Qi, Gabriele Sadowski, and Defang Ouyang
5.1 Introduction of Solid Dispersion 81
5.2 Preparation Methods for Solid Dispersions 83
5.3 Thermodynamics of Solid Dispersions 85
5.4 Molecular Structure of Amorphous Solid Dispersions 89
5.5 Physical Stability of Solid Dispersions 91
5.6 Future Prospects 97
6 Computer Simulations of Lipid Membranes and Liposomes for Drug?@Delivery 101
David William ONeill, Sang Young Noh, and Rebecca Notman
6.1 Introduction 101
6.2 Methodological Considerations 102
6.3 Model Membranes 105
6.4 Small Molecule Uptake and Permeation across Membranes 108
6.5 NanoparticleMembrane Interactions 111
6.6 Mechanisms of Action of Chemical Penetration Enhancers 114
6.7 Future Challenges 116
7 Molecular Modeling for Protein Aggregation and Formulation 123
Dorota Roberts, Jim Warwicker, and Robin Curtis
7.1 Introduction 123
7.2 Protein Aggregation Pathways in Liquid Formulations 127
7.3 ProteinCosolvent Interactions 129
7.4 ProteinProtein Interactions 133
7.5 Informatics Studies of Protein Aggregation 136
7.6 Future Prospects 140
8 Computational Simulation of Inorganic Nanoparticle Drug Delivery Systems at the Molecular Level 149
Xiaotian Sun, Zhiwei Feng, Tingjun Hou, and Youyong Li
8.1 Introduction 149
8.2 Materials and Methods 152
8.3 Summary 164
9 Molecular andAnalytical Modeling of?@Nanodiamond for Drug Delivery?@Applications 169
Lin Lai and Amanda S. Barnard
9.1 Introduction 169
9.2 Structure of Individual NDs 170
9.3 Surface Chemistry and Interactions 172
9.4 NDs as a Therapeutic Platform 187
9.5 Outlook 189
10 Molecular Modeling of Layered Double Hydroxide Nanoparticles for?@Drug Delivery 197
Vinuthaa Murthy, Zhi Ping Xu, and Sean C. Smith
10.1 Introduction 197
10.2 Basic Structure of LDH 198
10.3 Synthesis of LDH 199
10.4 Molecular Modeling Methodology 200
10.5 Conclusions 214
11 Molecular Modeling as a Tool to Understand the Role of Poly(Ethylene) Glycol in Drug Delivery 217
Alex Bunker
11.1 PEGylation in Drug Delivery 217
11.2 A Brief History of the Computational Modeling of PEG 220
11.3 Molecular Modeling Applied to the Role PEG Plays in Drug Delivery 221
11.4 Future Directions 224
12 3D Structural Investigation of?@Solid?@Dosage Forms 235
Xianzhen Yin, Li Wu, You He, Zhen Guo, Xiaohong Ren, Qun Shao, Jingkai Gu, Tiqiao Xiao, Peter York, and Jiwen Zhang
12.1 Structural Architectures of Solid Dosage Forms and Methods of Investigation an Overview 235
12.2 Synchrotron Radiation X?]Ray Computed Microtomography 239
12.3 Principles and Procedures for SR?] Studies 239
12.4 3D Visualization and Quantitative Characterization 245
12.5 Future Prospects 258
13 Physiologically Based Pharmacokinetic Modelling in Drug Delivery 263
Raj K. Singh Badhan
13.1 Introduction 263
13.2 Modelling and Simulation Process 264
13.3 Pharmacokinetic Principles 264
13.4 Pharmacokinetic Modelling Approaches 267
13.5 Pharmacokinetic Software for Modelling 270
13.6 Developing a PBPK Model for an Orally Dosed Compound 270
13.7 Developing the Model 280
13.8 Summary 286
References 286
Index 293
