Crystal Morphology

A crystalline species is defined as a solid that is composed of atoms, ions or molecules arranged in a periodic, three-dimensional pattern. A three-dimensional array is called a lattice as shown in Figure 7. The requirement of a lattice is that each volume, which is called a unit cell is surrounded by identical objects. Three vectors, a, b, and c, are defined in a right-handed sense for a unit cell. However, since three vectors are quite arbitrary a unit cell is described by six scalars, a, b, c, a, (¡, and y without directions (Fig. 8). Several kinds of unit cells are possible, for example, if a = b = c and a = fi = y = 90°, the unit cell is cubic. It turns out that only seven different kinds of unit cells are necessary to include all the possible lattices. These correspond to the seven crystal systems as shown in Table 7.

The seven different point lattices can be obtained simply by putting points at the corners of the unit cells of the seven crystal systems. However, there are more possible arrangements of points, which do not violate the requirements of a lattice.

A crystalline particle is characterized by definite external and internal structures. Habit describes the external shape of a crystal, whereas polymorphic state refers to the definite arrangement of molecules inside the crystal lattice. Crystallization is invariably employed as the final step for purification of a solid. Use of different solvents and processing conditions may alter the habit of recrystallized particles, besides modifying the polymorphic state of the solid. Subtle changes in crystal habit at this stage can lead to significant variation in raw material

FIGURE 8 Scalars of lattice structure.

characteristics. Furthermore, various indices of dosage form performance such as particle orientation, flowability, packing, compaction, suspension stability, and dissolution can be altered even in the absence of significantly altered polymorphic state. These effects are a result of the physical effect of different crystal habits. In addition, changes in crystal habit accompanied with or without polymorphic transformation during processing or storage can lead to serious implications of physical stability in dosage forms. Therefore to minimize variations in raw material characteristics, to ensure reproducibility of results during preformu-lation, and to correctly judge the cause of instability and poor performance of a dosage form, it is essential to recognize the importance of changes in crystal surface appearance and habit of pharmaceutical powders.

The crystal habit is also affected by impurities present in the solution crystallizing; often these impurities provide the earliest nucleation of crystal growth and become integral part of the crystal. In some instances presence of impurities inhibit crystal growth as shown when certain dyes or heavy metals are mixed with solutions. If an impurity can adsorb at the growing

TABLE 7 Seven Crystal Systems

Crystal System

Axial lengths and angles

Cubic

a = b =c

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