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Cryst. Growth Des., Vol. 8, No. 7, 2008
Book ReViews Polymorphism in the Pharmaceutical Industry. Edited by Rolf Hilfiker. Weinheim, Germany. 2006. $215. 978-3-527-31146-0. It is now well understood that the solid-state structure adopted by a substance upon crystallization exerts a strong effect on the properties of that system, such as heat capacity, conductivity, volume, density, viscosity, surface tension, diffusivity, crystal hardness, crystal shape and color, refractive index, electrolytic conductivity, melting or sublimation properties, latent heat of fusion, heat of solution, solubility, dissolution rate, enthalpy of transitions, phase diagrams, stability, hygroscopicity, and rates of reactions. Knowledge of these effects has dramatically changed drug development, and questions of crystal structure and polymorphism have become vitally important to the pharmaceutical industry. In the 15 chapters of this book, important issues related to crystal forms are covered in detail. The first chapter of Polymorphism in the Pharmaceutical Industry entitled “Relevance of Solid-State Properties for Pharmaceutical Products” (R. Hilfiker, F. Blatter, and M. von Raumer) presents an overview of the importance of polymorphism to the industry, touching on issues of development phases, salt selection, crystal form screening, process development, and formulation. This chapter is followed by an exposition of the thermodynamics of polymorphs (S. Lohani and David J. W. Grant) that summarizes energetic relationships, enantiotropic and monotropic properties, and phase diagrams. A number of methodology chapters, whose titles are selfexplanatory in describing their content, follow the introductory section. In these contributions, the pros and cons of particular techniques are highlighted, and are illustrated through the use of appropriate examples. In this section, one finds the chapters “Characterization of Polymorphic Systems Using Thermal Analysis” (D. Q. M. Craig), “Solid-State NMR Spectroscopy” (J. W. Lubach and E. Munson), “Vibrational Spectroscopic Methods in Pharmaceutical Solid-State Characterization” (J. M. Chalmers and G. Dent), “Crystallography for Polymorphs” (P. Ochsenbein and K. J. Schenk), and “Light Microscopy” (G. Nichols). The importance of solvates and hydrates is covered next by U. J. Griesser, who discusses the classification of solvate types, how one goes about obtaining these, how such crystal forms are processed, and the relevance of these materials in a program of drug development. This chapter flow nicely into the next, where the important issue of hygroscopicity in crystal forms is reviewed by S. M. Reutzel-Edens and A.W. Newman. The
authors classify types of hygroscopic behavior and the scope of water-solid interactions, discuss the methodology for such studies, and relate the sorption properties to the crystallographic solids. The next chapter covers important aspects of the amorphous state (S. Petit and G. Coquerel), and provides strong discussions as to methods of preparation and stability. The following two chapters cover issues related to the identification of crystal forms in the solid-state space of a substance, namely, “Approaches to Polymorphism Screening” (R. Hilfiker, S. M. De Paul, and M. Szelagiewicz) and “Salt Selection” (P. H. Stahl and B. Sutter). Both chapters are extremely practical in their coverage and provide excellent guidance into the conduct of the respective programs. These chapters are followed by a excellent discussion of the development scientist’s worst nightmare, “Processing-Induced Phase Transformations and Their Implications on Pharmaceutical Product Quality” (R. Govindarajan and R. Suryanarayanan). The penultimate chapter in the book provides a view of polymorphic litigation from Joel Bernstein’s point of view and is a fascinating read through some of the landmark cases that have come to define the legal aspects of polymorphism in pharmaceutical solids. The final chapter in the book, “Scientific Considerations of Pharmaceutical Solid Polymorphism in Regulatory Applications” (S. P. F. Miller, A. S. Raw, and L. X. Yu), treats the all-important issues associated with registration and regulatory approval of drug entitles capable of existing in multiple crystal forms. This book presents a comprehensive coverage of topics that are extremely important to the development of polymorphic compounds having pharmaceutical interest and represents an important addition to the other two books already published on the subject. The depth of coverage brings the reader up to the state of the art in 2006, and provides a good overview of the numerous issues that developmental scientists must address as they bring chemical entities along the pathway of molecule to drug candidate to drug substance to drug product. It goes without saying that any materials science researcher in the pharmaceutical field will necessarily have to have a copy of this book on hand for ready reference. Harry G. Brittain Center for Pharmaceutical Physics, Milford, NJ
10.1021/cg800538r CCC: $40.75 2008 American Chemical Society Published on Web 06/14/2008
CG800538R 10.1021/cg800538r
