Supramolecular Synthons in Crystal Engineering of Pharmaceutical Properties by Nangia, Ashwini K.;

Rövid leírás:

This comprehensive resource skillfully consolidates Crystal Engineering, the design of organic solids, and Supramolecular Synthons (i.e. structural hydrogen bond units) to achieve desired Pharmaceutical Properties, including solubility, dissolution, bioavailability, permeability, particle size, tableting, hydration, and mechanical strength.

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Hosszú leírás:

This comprehensive resource skillfully consolidates crystal engineering, the design of organic solids, and supramolecular synthons (i.e., structural hydrogen bond units) to achieve desired pharmaceutical properties, including solubility, dissolution, bioavailability, permeability, particle size, tableting, hydration, and mechanical strength. Covering 30 years of crystal engineering developments and pharmaceutical applications, this book will be a single and complete resource for supramolecular and structural chemists, the crystal engineering community, pharmaceutical scientists, and industrial researchers.

Key Features

• Covers the fundamentals of crystal engineering and supramolecular synthons.
• Details the challenges of low solubility and low permeability facing oral drug formulations.
• Explains how heterosynthons provide a rational approach to address and implement solutions.
• Provides case studies from academic and industrial labs to walk the reader through the actual steps.
• Explores developments in the scale up and manufacture of crystal forms in pharmaceutical industry.

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Tartalomjegyzék:

Chapter 1 Introduction to Supramolecular Chemistry and Crystal Engineering

1.1 Introduction

1.2 Organic synthesis

1.3 Supramolecular chemistry

1.4 Crystal engineering

1.5 Hydrogen bonding

1.6 Space groups

1.7 Summary conclusions

1.8 References

1.9 Questions and thoughts

1.10 Additional reading

Chapter 2 Crystal Engineering, Supramolecular Synthons, and Cocrystal Design

2.1 Introduction

2.2 Supramolecular synthons

2.3 Crystal engineering of pharmaceutical cocrystals

2.3.1 Cocrystals

2.3.2 Pharmaceutical cocrystals

2.4 Cocrystal design approaches

2.4.1 Hydrogen bond synthons

2.4.2 ΔpK_a rule

2.4.3 Computational methods

2.4.4 Molecular electrostatic potential surface energy

2.4.5 Hansen solubility parameter

2.5 Summary conclusions

2.6 References

2.7 Questions and thoughts

Chapter 3 Pharmaceutical Solid-State Forms

3.1 Introduction

3.2 Pharmaceutical multi-component crystals

3.2.1 Drug salts and pharmaceutical cocrystals

3.2.2 Pharmaceutical cocrystals via crystal engineering

3.2.3 Coamorphous solids

3.2.4 Solid solutions and eutectics

3.2.5 Ionic liquids

3.2.6 Ionic cocrystals

3.2.7 Nanocrystalline drugs

3.2.8 Supramolecular gels of drugs

3.2.9 Salt−cocrystal continuum or hybrid quasi-state of proton

3.2.10 Cocrystal polymorphs

3.2.11 Ternary and higher organic cocrystals

3.3 Summary conclusions

3.4 References

3.5 Questions and thoughts

Chapter 4 Design and Methodology of Pharmaceutical Cocrystals

4.1 Introduction

4.2 Complementarity between API and coformer

4.3 Preparation methods of cocrystals

4.3.1 Spray drying

4.3.2 Freeze drying

4.3.3 Hot melt extrusion

4.3.4 Rotary evaporator method

4.3.5 Vapor-assisted tumbling

4.4 Drug−drug cocrystals

4.5 Drug−nutraceutical cocrystals

4.6 Ternary and higher order cocrystals

4.7 Cocrystals of different stoichiometry

4.8 Zwitterionic cocrystals

4.9 Halogen-bonded pharmaceutical cocrystals

4.10 Characterization methods of cocrystals

4.11 Summary conclusions

4.12 References

4.13 Questions and thoughts

Chapter 5 Applications of Pharmaceutical Cocrystals

5.1 Introduction

5.2 Bioavailability improvement

5.3 Hydration stability

5.4 Chemical degradation stability

5.5 Tableting

5.6 Mechanical properties

5.7 Phase diagram and solubility measurements

5.8 Permeability and plasma concentration

5.9 Spring and Parachute model

5.10 Summary conclusions

5.11 References

5.12 Questions and thoughts

Chapter 6 Continuous Manufacturing of Cocrystals and Salts

6.1 Introduction

6.2 Batch and flow chemistry

6.3 Flow chemistry and pharmaceutical cocrystals manufacturing

6.4 Case studies of pharmaceutical cocrystals and salts

6.5 Continuous process technologies

6.6 Flow guide for the synthetic chemist

6.7 Summary conclusions

6.8 References

6.9 Questions and thoughts

Chapter 7 Commercial Outlook of Pharmaceutical Cocrystals

7.1 Introduction

7.2 Present status

7.3 Patenting and regulatory aspects

7.4 Entresto® drug-drug cocrystal salt

7.5 Seglentis® US-FDA approval

7.6 Summary conclusions

7.7 References

7.8 Questions and thoughts

Chapter 8 Controlling Polymorphism

8.1 Introduction

8.2 Definition and importance

8.3 Polymorphism and cocrystallization

8.4 Tailored additives to control crystal size and morphology

8.5 Summary conclusions

8.6 References

8.7 Questions and thoughts

Chapter 9 Supramolecular Heterosynthon in High Bioavailability Drugs

9.1 Introduction

9.2 Common heterosynthons in drugs

9.3 Heterosynthon model for high bioavailability drugs

9.4 Models for permeability enhancement

9.5 Cocrystal drugs beyond the Rule of 5

9.6 Improving cell penetration by atom replacement

9.7 Summary conclusions

9.9 Questions and thoughts

Chapter 10 Other Applications of Cocrystals

10.1 Introduction

10.2 Property engineering

10.3 Mechanochemistry

10.4 Energetic cocrystals

10.5 Summary conclusions

10.6 References

10.7 Questions and thoughts

Chapter 11 AI ML ChatGPT in Chemistry

11.1 Introduction

11.2 Retrosynthetic reaction prediction

11.3 Medicinal molecules

11.4 MOFs and inorganic materials

11.5 Cocrystals

11.6 Summary conclusions

11.7 References

11.8 Questions and thoughts

Chapter 12 3D Electron Diffraction

12.1 Introduction

12.2 Advantages of ED

12.3 Resurgence of ED

12.4 New pharmaceutical challenges solved by ED

12.5 Summary conclusions

12.6 References

12.7 Questions and thoughts

Chapter 13 Challenges, Conclusions, and Future Directions

13.1 Introduction

13.2 Carboxamide−pyridine-N-oxide heterosynthon

13.3 Browsing the literature

13.4 Challenges in pharmaceutical cocrystal technology

13.5 Conclusions

13.6 References

13.7 Suggested reading

Index

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