[eBook Code] Characterization of Pharmaceutical Nano- and Microsystems (eBook Code, 1st)

List of Contributors xiii

Series Preface xvii

List of Abbreviations xix

1 Selecting a Particle Sizer for the Pharmaceutical Industry 1
Margarida Figueiredo, M. José Moura and Paulo J. Ferreira

1.1 Introduction 1

1.2 Particle Size Distribution 3

1.3 Selecting a Particle Sizer 8

1.4 Aspects of Some Selected Methods 13

1.5 Conclusions 22

2 Spectroscopic Methods in Solid-state Characterization 27
Clare Strachan, Jukka Saarinen, Tiina Lipiainen, Elina Vuorimaa-Laukkanen, Kaisa Rautaniemi, Timo Laaksonen, Marcin Skotnicki and Martin Dracínsky

2.1 Solid-state Structure of Particulates 27

2.2 Spectroscopy Overview 28

2.3 Spectroscopic Data Analysis 30

2.4 Infrared Spectroscopy 35

2.5 Near-infrared Spectroscopy 40

2.6 Terahertz Spectroscopy 46

2.7 Raman Spectroscopy 50

2.8 Nonlinear Optics 59

2.9 Fluorescence Spectroscopy 65

2.10 Solid-state Nuclear Magnetic Resonance 71

2.11 Conclusions 82

3 Microfluidic Analysis Techniques for Safety Assessment of Pharmaceutical Nano- and Microsystems 97
Tiina M. Sikanen, Iiro Kiiski and Elisa Ollikainen

3.1 Microfluidic Bioanalytical Platforms 97

3.2 Microfabrication Methods and Materials 98

3.3 Microfluidic Cell Cultures 101

3.4 Immobilized Enzyme Microreactors for Hepatic Safety Assessment 109

3.5 Microfluidic Total Analysis Systems 120

3.6 Epilogue 126

4 In Vitro--In Vivo Correlation for Pharmaceutical Nano- and Microsystems 137
Preshita P. Desai and Vandana B. Patravale

4.1 Introduction 137

4.2 In Vitro Dissolution and In Vivo Pharmacokinetics 138

4.3 Levels of Correlation 143

4.4 Models of IVIVC 145

4.5 IVIVC Model Validation: Predictability Evaluation 150

4.6 IVIVC Development Step-by-Step Approach 151

4.7 Brief Introduction to Micro/Nanosystems and IVIVC Relevance 152

4.8 Applications of IVIVC for Micro/nanoformulations 158

4.9 Softwares Used for IVIVC 165

4.10 Conclusion and Future Prospects 166

5 Characterization of Bioadhesion, Mucin-interactions and Mucosal Permeability of Pharmaceutical Nano- and Microsystems 171
Ellen Hagesaether, Malgorzata Iwona Adamczak, Marianne Hiorth and Ingunn Tho

5.1 Introduction 171

5.2 Background and Theory 172

5.3 Mucosal Membranes 174

5.4 Use of Mucosal Membranes in Studies of Micro- and Nanoparticles 183

5.5 Selection of Biological Models 185

5.6 Methods for Testing Biocompatibility 189

5.7 Methods for Testing Mucoadhesion 190

5.8 Methods for Testing Mucopenetration 195

5.9 Methods for Assessing Cell Interactions 197

5.10 Concluding Remarks 203

6 Cell-Nanoparticle Interactions: Toxicity and Safety Issues 207
Flavia Fontana, Nazanin Zanjanizadeh Ezazi, Nayab Tahir and Helder A. Santos

6.1 Introduction 207

6.2 Mechanisms of NP-Induced Cellular Toxicity 211

6.3 In Vitro Assays to Evaluate Cell--NP Interactions 216

6.4 Metal Oxide Nanoparticles 217

6.5 Non-metallic Nanoparticles 223

6.6 Conclusions and Future Perspectives 235

7 Intestinal Mucosal Models to Validate Functionalized Nanosystems 243
Claudia Azevedo, Ines Pereira and Bruno Sarmento

7.1 Introduction 243

7.2 Intestinal Mucosal Characteristics 244

7.3 In Vitro Models 248

7.4 Ex Vivo Intestinal Models for In Vitro/In Vivo Correlation of Functionalized Nanosystems 258

7.5 In Situ Models 260

7.6 In Vivo Models 264

7.7 Conclusion 265

8 Biodistribution of Polymeric, Polysaccharide and Metallic Nanoparticles 275
Nazli Erdogar, Gamze Varan, Cem Varan and Erem Bilensoy

8.1 Introduction 275

8.2 Biodistribution and Pharmacokinetics 276

8.3 Mechanisms Affecting Biodistribution 277

8.4 Conclusion 285

9 Opportunities and Challenges of Silicon-based Nanoparticles for Drug Delivery and Imaging 291
Didem Sen Karaman, Martti Kaasalainen, Helene Kettiger and Jessica M. Rosenholm

9.1 Synthesis and Characteristics of Silica-based Nanoparticles 292

9.2 Solid-state Characterization 303

9.3 Medium-dependent Characterization 307

9.4 Incorporation of Active Molecules 314

9.5 Biorelevant Physicochemical Characterization 319

9.6 Conclusions 328

10 Statistical Analysis and Multidimensional Modeling in Research 339
Osmo Antikainen

10.1 Measurement in Research 339

10.2 Mean and Sample Mean 339

10.3 Correlation 341

10.4 Modeling Relationships Between Series of Observations 343

10.5 Quality of a Model 344

10.6 Multivariate Data 350

10.7 Principal Component Analysis (PCA) 362

10.8 Conclusions 366

References 366

Index 369