Computational Pharmaceutics

Dr Defang Ouyang is at the Institute of Medical Sciences, University of Macau in China as well as Aston University, UK. He has a multi-disciplinary and unique background and expertise in both drug delivery and molecular modeling. He completed his PhD at The University of Queensland, Australia in 2010. Since joining Aston, he has pioneered the application of molecular modeling techniques in the field of drug delivery - "computational pharmaceutics", including cyclodextrin-drug complexes, solid dispersions, non-viral gene delivery systems and liposome formulations. So far, he has authored over 20 refereed publications, consisting of an invited book, a book chapter, invited reviews, journal articles, conference papers and patents.Professor Sean C. Smith is at the School of Chemical Engineering, University of New South Wales, Australia. He was previously Director of the Center for Nanophase Materials Sciences at Oak Ridge National Laboratory, USA. He is firmly established internationally as a significant figure in the field of theoretical and computational chemistry. His contributions include theoretical studies of chemical reactions, material sciences, nano science and biological sciences. His publications include one book, three invited chapters, three invited reviews, and 203 refereed journal articles.

• List of Contributors xiSeries Preface xiiiPreface xvEditors' Biographies xvii1 Introduction to Computational Pharmaceutics 1Defang Ouyang and Sean C. Smith1.1 What Is Computational Pharmaceutics? 11.2 Application of Computational Pharmaceutics 31.3 Future Prospects 42 Crystal Energy Landscapes for Aiding@Crystal Form Selection 7Sarah L. Price2.1 Introduction 72.2 CSP Methods for Generating Crystal Energy Landscapes 102.3 Examples of the Use of Crystal Energy Landscapes as a Complement to@Solid Form Screening 182.4 Outlook 243 Solubilization of Poorly Soluble Drugs: Cyclodextrin]Based Formulations 31Sachin S. Thakur, Harendra S. Parekh, Carl H. Schwable, Yong Gan, and Defang Ouyang3.1 Cyclodextrins in Pharmaceutical Formulations –Overview 313.2 Drug]CD Complexes –Preparation Methods 353.3 Physicochemical Principles Underlying Drug]CD Complexes 363.4 Characterization of Drug]CD Complexes 383.5 Theoretical Progress of CD Studies 413.6 Future Prospects of Cyclodextrin Formulation 444 Molecular Modeling of Block Copolymer Self]Assembly and Micellar Drug Delivery 53Myungshim Kang, Dennis Lam, Dennis E. Discher, and Sharon M. Loverde4.1 Introduction 534.2 Simulation Methods 584.3 Simulations of Micellar Drug Delivery 634.4 Taxol 684.5 Summary and Conclusions 745 Solid Dispersion–a Pragmatic Method to Improve the Bioavailability of Poorly Soluble Drugs 81Peng Ke, Sheng Qi, Gabriele Sadowski, and Defang Ouyang5.1 Introduction of Solid Dispersion 815.2 Preparation Methods for Solid Dispersions 835.3 Thermodynamics of Solid Dispersions 855.4 Molecular Structure of Amorphous Solid Dispersions 895.5 Physical Stability of Solid Dispersions 915.6 Future Prospects 976 Computer Simulations of Lipid Membranes and Liposomes for Drug@Delivery 101David William O’Neill, Sang Young Noh, and Rebecca Notman6.1 Introduction 1016.2 Methodological Considerations 1026.3 Model Membranes 1056.4 Small Molecule Uptake and Permeation across Membranes 1086.5 Nanoparticle–Membrane Interactions 1116.6 Mechanisms of Action of Chemical Penetration Enhancers 1146.7 Future Challenges 1167 Molecular Modeling for Protein Aggregation and Formulation 123Dorota Roberts, Jim Warwicker, and Robin Curtis7.1 Introduction 1237.2 Protein Aggregation Pathways in Liquid Formulations 1277.3 Protein–Cosolvent Interactions 1297.4 Protein–Protein Interactions 1337.5 Informatics Studies of Protein Aggregation 1367.6 Future Prospects 1408 Computational Simulation of Inorganic Nanoparticle Drug Delivery Systems at the Molecular Level 149Xiaotian Sun, Zhiwei Feng, Tingjun Hou, and Youyong Li8.1 Introduction 1498.2 Materials and Methods 1528.3 Summary 1649 Molecular and Analytical Modeling of@Nanodiamond for Drug Delivery@Applications 169Lin Lai and Amanda S. Barnard9.1 Introduction 1699.2 Structure of Individual NDs 1709.3 Surface Chemistry and Interactions 1729.4 NDs as a Therapeutic Platform 1879.5 Outlook 18910 Molecular Modeling of Layered Double Hydroxide Nanoparticles for@Drug Delivery 197Vinuthaa Murthy, Zhi Ping Xu, and Sean C. Smith10.1 Introduction 19710.2 Basic Structure of LDH 19810.3 Synthesis of LDH 19910.4 Molecular Modeling Methodology 20010.5 Conclusions 21411 Molecular Modeling as a Tool to Understand the Role of Poly(Ethylene) Glycol in Drug Delivery 217Alex Bunker11.1 PEGylation in Drug Delivery 21711.2 A Brief History of the Computational Modeling of PEG 22011.3 Molecular Modeling Applied to the Role PEG Plays in Drug Delivery 22111.4 Future Directions 22412 3D Structural Investigation of@Solid@Dosage Forms 235Xianzhen Yin, Li Wu, You He, Zhen Guo, Xiaohong Ren, Qun Shao, Jingkai Gu, Tiqiao Xiao, Peter York, and Jiwen Zhang12.1 Structural Architectures of Solid Dosage Forms and Methods of Investigation– an Overview 23512.2 Synchrotron Radiation X]Ray Computed Microtomography 23912.3 Principles and Procedures for SR]μ Studies 23912.4 3D Visualization and Quantitative Characterization 24512.5 Future Prospects 25813 Physiologically Based Pharmacokinetic Modelling in Drug Delivery 263Raj K. Singh Badhan13.1 Introduction 26313.2 Modelling and Simulation Process 26413.3 Pharmacokinetic Principles 26413.4 Pharmacokinetic Modelling Approaches 26713.5 Pharmacokinetic Software for Modelling 27013.6 Developing a PBPK Model for an Orally Dosed Compound 27013.7 Developing the Model 28013.8 Summary 286References 286Index 293