Michael Gruss - Solid State Development and Processing of Pharmaceutical Molecules: Salts, Cocrystals, and Polymorphism

1. Chapter 1
2. Chapter 2
3. Chapter 3
4. Chapter 4-3
5. Chapter 4-5
6. Chapter 4-6
7. Chapter 4-8
8. Chapter 4-9
9. Chapter 4-10
10. Chapter 5
11. Chapter 6
12. Chapter 8
13. Chapter 9-2
14. Chapter 10

1. Chapter 1
2. Chapter 2
3. Chapter 3
4. Chapter 4-1
5. Chapter 4-2
6. Chapter 4-3
7. Chapter 4-4
8. Chapter 4-5
9. Chapter 4-6
10. Chapter 4-7
11. Chapter 4-8
12. Chapter 4-9
13. Chapter 4-10
14. Chapter 5
15. Chapter 6
16. Chapter 7
17. Chapter 8
18. Chapter 10
19. Chapter 11

Edited by

R. Mannhold, H. Buschmann, J. Holenz

Editorial Board

G. Folkers, H. Kubinyi, H. Timmerman, H. van de Waterbeemd, J. Bondo Hansen

Bachhav, Y. (Ed.)

Innovative Dosage Forms

Designs and Development at Early Stage

2019

ISBN: 9783527343966

Vol. 79

Gervasio, F. L., Spiwok, V. (Eds.)

Biomolecular Simulations in Structurebased Drug Discovery

2018

ISBN: 9783527342655

Vol. 75

Sippl, W., Jung, M. (Eds.)

Epigenetic Drug Discovery

2018

ISBN: 9783527343140

Vol. 74

Giordanetto, F. (Ed.)

Early Drug Development

2018

ISBN: 9783527341498

Vol. 73

Handler, N., Buschmann, H. (Eds.)

Drug Selectivity

2017

ISBN: 9783527335381

Vol. 72

Vaughan, T., Osbourn, J., Jalla, B. (Eds.)

Protein Therapeutics

2017

ISBN: 9783527340866

Vol. 71

Ecker, G. F., Clausen, R. P., and Sitte, H. H. (Eds.)

Transporters as Drug Targets

2017

ISBN: 9783527333844

Vol. 70

MarticKehl, M. I., Schubiger, P.A. (Eds.)

Animal Models for Human Cancer

Discovery and Development of Novel Therapeutics

2017

ISBN: 9783527339976

Vol. 69

Volume 79

Edited by
Michael Gruss

Volume Editor

Dr. Michael Gru
Solid State Concepts
Hermannstr. 8
52062 Aachen
Germany

Series Editors

Prof. Dr. Raimund Mannhold
Rosenweg 7
40489 Dsseldorf
Germany

Dr. Helmut Buschmann
Sperberweg 15
52076 Aachen
Germany

Dr. Jrg Holenz
GRT Therapeutics
Grunenthal Boston Pain Innovation Hub1 Broadway
Cambridge MA 02142
United States

Cover Illustration: Gunther Schulz using
iStock #17264342 / alwyncooper

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Print ISBN: 9783527346356
ePDF ISBN: 9783527823055
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Michael Gru works as an independent scientific consultant for the pharmaceutical, chemical, and nutrition industry, and he is known and well recognized as an expert in this field. During his industrial career, he conducted solidstate investigations on pharmaceutical drug substances and intermediates. He is author or coauthor of more than 15 patent applications in the field of salts, cocrystals, and polymorphs, and some of the drugs are globally marketed.

Polymorphism presents opportunities as well as challenges. Investigation of the properties of different forms of a commercial drug can lead to new products with improved onset time, greater bioavailability, sustained release properties, or other therapeutic enhancements. New forms can bring improvements in manufacturing costs or API purity.

The potential for solid form variation does not end at API production. Solid form issues remain through formulation, manufacture, storage, and use of drug product. It is common to observe form transformation during standard manufacturing operations like wet granulation and milling. Excipient interactions and compaction can induce form changes. Changes can occur in the final dosage form over time.

Whenever there is a specification failure in drug product or drug substance, solid form changes should be considered in the search for causes. Particularly, symptomatic is failure to meet melting point or dissolution specifications. Changes in humidity, crystallization conditions, or crystallization solvent can produce unwanted forms.

Due to the importance of solidphase characteristics in pharmaceutical industry, several brilliant review articles and books have been published.

The current volume entitled SolidState Development and Processing of Pharmaceutical Molecules in our book series Methods and Principles in Medicinal Chemistry is focused on specific aspects of salts, cocrystals, and polymorphism in drug development. The book compiles general concepts and their latest applications along with wellselected case studies considering experiences and publications from the last 10 to 12years. It considers new developments in science and knowledge that has been contributed by academic and industrial researchers during the last decade.

This book clearly goes beyond the classical description of solidstate properties. It encourages outofthebox thinking and allows a look beyond the science. In defining the scope of the book, one intention was to allow the identification of beneficial synergies for successful integration of solidstate form development workflows into general management strategies for R&D and production.

The editors would like to thank Michael and all contributing authors for such a successful compilation, which will stimulate the awareness of the impact of solidstaterelated topics and enhance the importance of salts, cocrystals, and polymorphic forms throughout the pharmaceutical value chain.