！Chapter 2－Crystallization of Organic Compounds.pdf

Chapter 2 Properties For pharmaceuticals and special fine organic chemicals, solution crystallization, in which solvents are used, is the primary method of crystallization, in comparison to other crystalli- zation techniques such as melt or supercritical crystallization. The goal of this chapter is to introduce basic properties of solution and crystals in order to better understand, design, and optimize the crystallization processes. The relevance of these basic properties to crystal qual- ities and crystallization operations will be highlighted, accompanied with specific examples. With regard to specific properties, we will focus on those that are more relevant to sol- ution crystallization and those that have a direct impact on the quality of the final bulk phar- maceuticals such as purity, form, habit, and size, based upon our own experience. We will leave readers to find other properties, such as miller index for crystal morphology, hardness of crystals, interfacial tension, etc., in other books on crystallization (Mersmann 2001; Mullin 2001), which provide in-depth theoretical discussion on these properties. 2.1 SOLUBILITY Understanding the solubility behavior is an indispensable requirement for the successful development of crystallization processes. It is necessary to know how much solute can dis- solve in the solvent system initially and how much solute will remains in the solvent at the end in order to conduct the crystallization operation. For solution crystallization, solubility of a chemical compound is simply the equilibrium (maximum) amount of this compound that can dissolve in a specific solvent system. A solution is saturated if the solute concentration is at its solubility limit. At saturation, no more dissolution will occ