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Crystalline and Amorphous Solids
C H A P T E R
2 Crystalline and Amorphous Solids Geoff G. Z. Zhang and Deliang Zhou
2.1 INTRODUCTION
shape, or habit, or morphology of the particles, where the internal structures that make up the solid particles remain the same. Although important for pharmaceutical development, these are not discussed in this chapter. The focus of this chapter is on solids with distinct differences in their internal structure. Based on the degree of long-range order/periodicity, solids are categorized into three groups. Amorphous phases are those solids that do not exhibit long-range order in any of the three physical dimensions. However, short-range order could exist for amorphous solids. Because of the importance of this class of solids to pharmaceutical development, it is discussed in detail in Section 2.7. If materials have long-range order in only one or two dimensions, they are liquid crystalline in nature. Liquid crystalline materials can be further categorized, based on the number of components contained therein, as is the case for crystalline solids. Since liquid crystals, with properties intermediate to conventional liquids and three-dimensional solids, are not frequently encountered, they will not be discussed in detail. The vast majority of pharmaceutical solids fall into the category of crystalline solids, because they exhibit longrange order in all three dimensions. Crystalline solids can be further categorized into various sub-types based on the number of components that make up the solid internally, in a homogeneous fashion. The solid could be composed of the drug alone, or as adducts with one (binary), two (ternary), three (quaternary), etc. … other chemical species. Although the number of other chemical species, apart from the drug itself, can increase without limit, it usually is a relatively low integer.
Of the several states of matter in which a substance can reside, the solid state is most commonly encountered and, therefore, the most important and relevant state for pharmaceutical development. Most of the pharmaceutical products on the market or formulations presently being developed are solid dosage forms. Even when a product is marketed or developed as a solution or a semi-solid formulation, a solid is usually selected and manufactured as an active pharmaceutical ingredient (API) for reasons such as the ability to crystallize and therefore to be purified, ease of handling, better chemical stability in comparison with liquids, etc. Therefore, understanding of various solid forms that may occur, as well as the rational selection of solid forms for development, is critical to the facile development of a particular chemical entity. Many books1–7 and special journal issues8–12 are devoted to this topic. This chapter, due to limitation of space, provides only a brief introduction to the fundamental principles and practical aspects of pharmaceutical solids. Interested readers are encouraged to read the books and reviews cited above.
2.2 DEFINITIONS AND CATEGORIZATION OF SOLIDS The various types of pharmaceutical solids are shown in Figure 2.1. Solids can show differences externally or internally. External differences are referred to as the
Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice
25
© 2009, Elsevier Inc.
2 Crystalline and Amorphous Solids Geoff G. Z. Zhang and Deliang Zhou
2.1 INTRODUCTION
shape, or habit, or morphology of the particles, where the internal structures that make up the solid particles remain the same. Although important for pharmaceutical development, these are not discussed in this chapter. The focus of this chapter is on solids with distinct differences in their internal structure. Based on the degree of long-range order/periodicity, solids are categorized into three groups. Amorphous phases are those solids that do not exhibit long-range order in any of the three physical dimensions. However, short-range order could exist for amorphous solids. Because of the importance of this class of solids to pharmaceutical development, it is discussed in detail in Section 2.7. If materials have long-range order in only one or two dimensions, they are liquid crystalline in nature. Liquid crystalline materials can be further categorized, based on the number of components contained therein, as is the case for crystalline solids. Since liquid crystals, with properties intermediate to conventional liquids and three-dimensional solids, are not frequently encountered, they will not be discussed in detail. The vast majority of pharmaceutical solids fall into the category of crystalline solids, because they exhibit longrange order in all three dimensions. Crystalline solids can be further categorized into various sub-types based on the number of components that make up the solid internally, in a homogeneous fashion. The solid could be composed of the drug alone, or as adducts with one (binary), two (ternary), three (quaternary), etc. … other chemical species. Although the number of other chemical species, apart from the drug itself, can increase without limit, it usually is a relatively low integer.
Of the several states of matter in which a substance can reside, the solid state is most commonly encountered and, therefore, the most important and relevant state for pharmaceutical development. Most of the pharmaceutical products on the market or formulations presently being developed are solid dosage forms. Even when a product is marketed or developed as a solution or a semi-solid formulation, a solid is usually selected and manufactured as an active pharmaceutical ingredient (API) for reasons such as the ability to crystallize and therefore to be purified, ease of handling, better chemical stability in comparison with liquids, etc. Therefore, understanding of various solid forms that may occur, as well as the rational selection of solid forms for development, is critical to the facile development of a particular chemical entity. Many books1–7 and special journal issues8–12 are devoted to this topic. This chapter, due to limitation of space, provides only a brief introduction to the fundamental principles and practical aspects of pharmaceutical solids. Interested readers are encouraged to read the books and reviews cited above.
2.2 DEFINITIONS AND CATEGORIZATION OF SOLIDS The various types of pharmaceutical solids are shown in Figure 2.1. Solids can show differences externally or internally. External differences are referred to as the
Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice
25
© 2009, Elsevier Inc.