Disordered Pharmaceutical Materials (eBook)

Marc Descamps is Professor for solid state physics at the University of Lille, France, where he initiated the Therapeutic Materials Group. He is the author of more than 180 publications in international journals and he has collaborated with several large pharmaceutical companies. His research interests include: phase transitions in molecular materials, disordered crystals, molecular glasses and studies of the structural and dynamic properties of pharmaceutical solids by a variety of physicochemical techniques. Recently he focused his research on the effects of the mechanical activation of pharmaceuticals.

1 Some Facets of Molecular Disorder in Crystalline and Amorphous Pharmaceuticals 1
Marc Descamps and Jean-François Willart
1.1 The Crystal/Amorph Alternative 2
1.2 Characteristics of the Disorder in Glass Formers 28
Acknowledgments 51
References 51
2 Influence of Disorder on Dissolution 57
Khushboo Kothari and Raj Suryanarayanan
2.1 Introduction 57
2.2 Approaches to Enhance Solubility 59
2.3 Measuring the Solubility Advantage of Amorphous Compounds 64
2.4 Solid Dispersions 66
2.5 Polymer Properties 67
2.6 Drug?Polymer Interactions 70
2.7 Polymer Concentration 71
2.8 Other Formulation Components 73
2.9 Formulation Variables 74
2.10 Reliable Measurement of Supersaturation 75
2.11 Conclusion 76
References 77
3 Crystal Imperfections in Molecular Crystals: Physical and Chemical Consequences 85
William Jones and Mark D. Eddleston
3.1 Introduction 85
3.2 General Aspects of Defects in Crystals 87
3.3 Role of Imperfections in Reactivity and Stability ? Chemistry in the
Perfect and Imperfect Lattice 92
3.4 Role in Physical Processes 96
3.5 Concluding Remarks 99
References 99
4 Observation and Characterization of Crystal Defects in Pharmaceutical Solids 103
Mark D. Eddleston andWilliam Jones
4.1 Introduction 103
4.2 Techniques for Characterizing Defects within Crystals 104
4.3 Techniques for Characterizing Defects Emergent at Crystal Surfaces 119
4.4 Techniques for Quantifying Defect Densities within Crystals 125
4.5 The Complementarity of Techniques for Characterizing Defects 126
4.6 Summary and Outlook 127
Acknowledgment 128
References 128
5 "Enantiomeric Disorder" Pharmaceutically Oriented 135
Gerard Coquerel and Rui Tamura
5.1 Introduction 135
5.2 Introduction and Lexicon of Specific Terms Used among Chiral Molecules and Chiral Molecular Associations 135
5.3 Restrictions in Symmetry Operations Inside Crystal Lattices with an Enantiomeric Excess Different from Zero 136
5.4 Impact of Chirality on Phase Diagrams and the Gibbs?Scott Phase Rule 137
5.5 Competitions between Solid Solutions (Impact of Polymorphism on Solid Solutions) Application: Preferential Enrichment 149
5.6 Disorder at Level 3 Multiepitaxy between Enantiomers 154
5.7 Conclusion and Perspectives 156
Acknowledgments 157
References 157
6 Conformational Disorder and Atropisomerism in Pharmaceutical Compounds 161
Attilio Cesàro, Barbara Bellich, Giovanna Giannini, and Alessandro Maiocchi
6.1 Premise: Conformational Energy Barriers in FlexibleMolecules 161
6.2 Conformational Topology and Crystallization of Chain Molecules 162
6.3 Conformational Polymorphism and Crystallization of Flexible Molecules 165
6.4 Conformational Flexibility of Ring Molecules: Carbohydrates 170
6.5 Hindered Conformational Isomerism: Atropisomerism 172
6.6 Conclusion 178
Acknowledgments 180
References 180
7 Tautomerism in Drug Delivery 183
Zaneta Wojnarowska and Marian Paluch
7.1 Broadband Dielectric Spectroscopy as a Powerful Tool for Investigating the Tautomerization Process in Condensed Materials 187
7.2 Tautomerization Kinetics of Supercooled Pharmaceuticals 190
Acknowledgment 197
References 198
8 Disorders in Pharmaceutical Polymers 201
Emeline Dudognon and Sheng Qi
8.1 Polymers Architectures - Structural Disorders 202
8.2 Structural States and Phases Transitions 205
8.3 Dynamic Disorders 213
8.4 Blends of Polymer and Small Molecules 221
8.5 Effect of the Structural Properties of Pharmaceutical Polymers on Their Physical Behavior 224
8.6 Concluding Remarks 234
References 235
9 Polymer Gels, Hydrogels, and Scaffolds ? An Overview 241
Madeleine Djabourov and Kawthar Bouchemal
9.1 Introduction 241
9.2 Gels and Hydrogels 243
9.3 Scaffolds 268
9.4 Conclusion 275
References 276
10 Use of the Pair Distribution Function Analysis in the Context of Pharmaceutical Materials 283
Pierre Bordet and PaulineMartinetto
10.1 Introduction 283
10.2 What Is the PDF? 284
10.3 How to Measure the PDF 288
10.4 Modeling of the PDF 290
10.5 Applications of PDF Analysis to Molecular and Pharmaceutical Compounds 292
10.6 Conc