Pharmaceutical Salts and Co-crystals (RSC Drug Discovery, 16) - Hardcover

Hardcover

ISBN 10: 1849731586 ISBN 13: 9781849731584

Verlag: Royal Society of Chemistry, 2011

Inhaltsangabe

From crystal structure prediction to totally empirical screening, the quest for new crystal forms has become one of the most challenging issues in the solid state science and particularly in the pharmaceutical world. In this context, multi-component crystalline materials like co-crystals have received renewed interest as they offer the prospect of optimized physical properties. As illustrated in this first book_ entirely dedicated to this emerging class of pharmaceutical compounds_ the outcome of such endeavours into crystal engineering have demonstrated clear impacts on production, marketing and intellectual property protection of active pharmaceutical ingredients (APIs). Indeed, co-crystallization influences relevant physico-chemical parameters (such as solubility, dissolution rate, chemical stability, melting point, hygroscopicity, à) and often offers solids with properties superior to those of the free drug. Combining both reports of the latest research and comprehensive overviews of basic principles, with contributions from selected experts in both academia and industry, this unique book is an essential reference, ideal for pharmaceutical development scientists and graduate students in pharmaceutical science.

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Über die Autorin bzw. den Autor

Johan Wouters is Professor at the Department of Chemistry and a Member of the Drug Design Discovery Center at the University of Namur, Belgium. He is also a teacher in general chemistry, crystallography and structure-based drug design and is the author of about 120 papers. Luc QuÚrÚ is at UCB, a global Biopharma, as head of Chemical Analytical Development. Current UCB strategy with respect to solid-state issues and opportunities has been developed under his leadership.

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Multi-component crystalline materials (salts and co-crystals) have received renewed interest in recent years due to their importance in the pharmaceutical industry. Pharmaceutical salts and co-crystals represent an emerging class of pharmaceutical materials offering the prospect of optimized physical properties giving new stable and patentable solid forms. Indeed these multi-component crystalline forms influence relevant physico-chemical parameters such as solubility, dissolution rate, chemical and physical stability, melting point and hygroscopicity, which can result in solids with properties superior to those of the free drug. This unique book focuses on the currently 'hot topic' of Pharmaceutical Salts and Co-crystals and covers the following key topics: the fundamental aspects of salts and co-crystals; the role of fluorine in weak interactions in co-crystals; polymorph prediction of small organic molecules, co-crystals and salts; shape and polarity in co-crystal formation; the role of co-crystals in pharmaceutical development; solid forms and pharmacokinetics; the application of mechanochemistry in the synthesis and discovery of new pharmaceutical forms; co-crystallization in solution and scale-up; analytical techniques and strategies for salt/co-crystal characterization; co-crystal solubility and thermodynamic stability; application of phase diagrams in co-crystal search and preparation; limits of the co-crystal concept and beyond; commercial opportunities and patent considerations; using Piracetam as a learning model and monographs of the most frequent co-crystal formers. Combining both reports of the latest academic research and comprehensive overviews of basic principles, with more applied contributions from selected experts in industry. This blend of expertise makes this book an essential reference for pharmaceutical development scientists, researchers in crystal engineering, and is equally useful for the more seasoned expert as well as for the graduate student.

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Pharmaceutical Salts and Co-crystals

By Johan Wouters, Luc Quéré

The Royal Society of Chemistry

Copyright © 2012 Royal Society of Chemistry
All rights reserved.

ISBN: 978-1-84973-158-4

Contents

Chapter 1 Pharmaceutical Salts and Co-crystals: Retrospect and Prospects Gautam R. Desiraju, 1, 
Chapter 2 Fundamental Aspects of Salts and Co-crystals Andrew D. Bond, 9, 
Chapter 3 Role of Fluorine in Weak Interactions in Co-crystals Seetha Lekshmi Sunil, Susanta K. Nayak, Venkatesha R. Hathwar, Deepak Chopra and Tayur N. Guru Row, 29, 
Chapter 4 Polymorph Prediction of Small Organic Molecules, Co-crystals and Salts Frank J. J. Leusen and John Kendrick, 44, 
Chapter 5 Shape and Polarity in Co-crystal Formation: Database Analysis and Experimental Validation L. Fábián and T. Friscic, 89, 
Chapter 6 Role of Co-crystals in the Pharmaceutical Development Continuum Nate Schultheiss and Jan-Olav Henck, 110, 
Chapter 7 Solid Forms and Pharmacokinetics N. Biswas, 128, 
Chapter 8 Application of Mechanochemistry in the Synthesis and Discovery of New Pharmaceutical Forms: Co-crystals, Salts and Coordination Compounds Tomislav Friscic and William Jones, 154, 
Chapter 9 Co-crystallization in Solution and Scale-up Issues E. Gagnière, D. Mangin, S. Veesler and F. Puel, 188, 
Chapter 10 Analytical Techniques and Strategies for Salt/Co-crystal Characterization Susan M. Reutzel-Edens, 212, 
Chapter 11 Co-crystal Solubility and Thermodynamic Stability L. Roy, M.P. Lipert and N. Rodríguez-Hornedo, 247, 
Chapter 12 Application of Phase Diagrams in Co-crystal Search and Preparation Timo Rager and Rolf Hilker, 280, 
Chapter 13 Limits of the Co-crystal Concept and Beyond Gerard Coquerel, 300, 
Chapter 14 Co-crystals: Commercial Opportunities and Patent Considerations Marcel Hoffman and Jeffrey A. Lindeman, 318, 
Chapter 15 Concluding Remarks using Piracetam as a Learning Model Johan Wouters, Anaelle Tilborg and Luc Quéré, 330, 
Chapter 16 Monographs of most Frequent Co-Crystal Formers Johan Wouters, Sandrine Rome and Luc Quéré, 338, 
Subject Index, 383, 

CHAPTER 1

Pharmaceutical Salts and Co-crystals: Retrospect and Prospects

GAUTAM R. DESIRAJU

Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India

Every new field in chemistry needs a link to an application of commercial and practical use to sustain interest. Each such field generates a whole new set of ideas, paradigms and models. These concepts need to be tested in as wide a variety of forums as possible because their generality has to be proved. The industrial enterprise has always provided an excellent testing ground for new ideas in the chemical sciences. Many fundamental concepts took root because of an impetus from industry, the most spectacular ones being the discovery of stereochemistry by Pasteur, Haber's process for nitrogen fixation, and the birth of polymer chemistry starting with the production of synthetic rubber from isoprene. The subject of crystal engineering appeared in its modern manifestation in the late 1980s and early 1990s. Two important branches of this subject emerged. The field of co-ordination polymers quickly found its practical application in the gas absorption properties of metal-organic framework compounds. The field of organic crystal engineering found its practical application, a little later, in the area of pharmaceutical co-crystals and salts. The chapters in this book illustrate the tremendous growth in this area during the past decade.

Co-crystals have been around in the chemical literature ever since Wöhler described quinhydrone in 1844. Pfeiffer's monumental work in 1922, Organische Molekulverbindungen now has a worthy successor in Herbstein's two volume magnum opus, Crystalline Molecular Complexes and Compounds, nearly a century later. What crystal engineering did was to provide a context wherein these compounds were given a name, co-crystals, however contentious it was. Secondly, it provided the formalism of the supramolecular synthon with which these compounds could be described, designed and deconvoluted. Finally it defined a setting in which these compounds could be assessed, namely in the pharmaceutical industry. The chapters in this book cover all the above aspects of research.

One might ask "What's in a name?". But names are important in chemistry, and there is usually much disputation about chemical names especially in areas that are still evolving. Some of us have defended or questioned the very term co-crystal. Coquerel, in his chapter in the present book, advises us in somewhat harsh terms when he says, "Therefore, rather than creating questionable terms and maintaining endless semantic debates with poor added values, the scientific community should concentrate more on the three long lasting problems ...". Now, I would tend to both agree and disagree with this view. While no discussion about nomenclature should be endless and there are indeed real practical scientific issues that need to be addressed, a part of this discussion about naming something in chemistry is about refining one's scientific ideas. Names in incompletely developed subjects keep changing and evolving. In the end, a name that survives, survives. Pfeiffer's Molekulverbindung and Herbstein's Molecular Compound are one and the same, but they are separated by a century of structural chemistry, an enormous time period in science. Bond's definition of a co-crystal as a multi-component molecular crystal has the great advantage of scientific accuracy with reasonable brevity but it lacks the pep and vigour of the term co-crystal. At the same time, one should not get carried away with style and ascribe scientific value to the term co-crystal. It has none. It is a bit like the term pseudopolymorph. In a recent perspective article, Bernstein levels criticism at this latter term, as being loose and lacking in scientific value. But the very same criticism can be applied to co-crystal, a term that the same author uses without flinching. My view is that both co-crystal and pseudopolymorph are of similar standing as far as the philosophy of nomenclature is concerned. Neither term has any real scientific value. Both terms are commonly used and in most cases there is little disagreement about whether or not a particular compound is a co-crystal or a pseudopolymorph. They are trivial names, as opposed to systematic names and, as I have written elsewhere, the trivial name sometimes survives. Few call acetic acid ethanoic acid. We shall have to wait and see if the term co-crystal is still extant 100 years from now.

What about pharmaceutical co-crystals? Zaworotko and co-workers defined these as "co-crystals that are formed between a molecular or ionic active pharmaceutical ingredient (API) and a co-crystal former that is a solid under ambient conditions". Bernstein, in the above-mentioned perspective article, criticises this term too and asks rhetorically if we would call something a pharmaceutical polymorph. But this is begging the question because in calling something a pharmaceutical co-crystal, one is moving away from science and going towards patent litigation. As Hoffman and Lindeman have argued in their chapter, it does not matter that every inventor uses the same definition of what is a co-crystal or, for that matter, a pharmaceutical co-crystal. A patentee may choose to define a term in any way in a patent specification and the patentee's definition controls the...

Details zur Ausgabe

• Verlag: Royal Society of Chemistry
• Erscheinungsdatum: 2011
• Sprache: Englisch
• ISBN 10: 1849731586
• ISBN 13: 9781849731584
• Einband: Gebundene Ausgabe
• Anzahl der Seiten: 406
• Herausgeber: Wouters Johan, Quéré Luc
• Kontakt zum Hersteller: Nicht verfügbar
• Verantwortliche Person: gpsr@libri.de; gpsr@libri.de; ; Europaallee 1; Bad Hersfeld; 36244; Deutschland