Inclusion and Occlusion

Inclusion or occlusion takes place when impurities or solvents are physically trapped within crystals. This simation is different from the case of solid compounds. In inclusion or occlusion, impurities can be occluded sporadically within crystals, whereas in solid compounds, impurities are distributed throughout the crystal lattice. While both inclusion and occlusion enclose solvent or impurities in the crystals, inclusion is more applicable to cases where solvents or impurities are trapped within crystal cavities during crystallization, whereas occlusion is more applicable to cases where surface liquid is trapped within crystal clusters or agglomerates during drying. In this book, the terms inclusion and occlusion will be used interchangeably. 

Inclusion can also occur in crystal agglomerates during crystaUization. Again, it is hypothesized that under rapid crystal growth conditions, particle-particle contact in the crystallizer slurry results in agglomerates of the original primary particles, and solvent can be trapped within the agglomerates. 

It may not be possible to observe the crystal cavities under the microscope. Nevertheless, based upon the authors experience, the level of residual solvent trapped within the crystal structure can be related to the degree of nucleation over crystal growth i.e., the higher the degree of nucleation, the higher the level of residual solvent. Example 

10-4 is a case study showing that the level of residual solvent can be related to the degree of nucleation over crystal growth. 

HPLC and GC analyses are two commonly used methods for determining the levels of impurities and residual solvent in the cake. Thermal gravimetric analysis is another very powerful tool. It detects not only the level of residual solvent, but also the temperature at which the solvent evaporates. If the cake weight loss due to solvent evaporation occurs at the melting point of the solid, this is a clear indication that solvent is trapped within the cake. 

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