Physical and Chemical Characterization of Granules

Physical property characterization of pharmaceutical granulations has been extensively reported in literature. Chemical properties are equally important due to their impact on specifications of a dosage form such as content uniformity, chemical 

Physical characterization can be performed at molecular, particulate, or bulk (macroscopic) levels. From the terminology cited by Brittain et al. (2), molecular properties are associated with individual molecules, particulate properties are considered as properties that pertain to individual solid particles, and bulk properties are those that are associated with an assembly of particulate species. Most reports in pharmaceutical literature cover characterization of bulk properties. 

Another technique to study particle morphology is scanning electron microscopy. Yoshinari et al. (4) studied morphological changes in granule shape with the addition of different amounts of granulating fluid (Fig. 1). 

Particle shape can be quantified by different methods. One popular method is through the use of Hey wood coefficients (5). The Hey wood shape coefficient is defined as the ratio of the surface shape coefficient (n for a sphere) to the volume shape coefficient (n/6 for a sphere) hence, the shape coefficient for a sphere would be 6.0. Applying this to a cube and using its projected area in its most stable position, the shape coefficient is 6.8. Cutting the cube in half in one dimension increases the shape factor to 9.0, whereas it increases to 26.6 if that cube was sliced one-tenth in one dimension. Further details of these types of calculations are provided by Rupp (5). 

Dry-sieve analysis is the easiest and the most convenient method for measuring granule size. The granulation is placed on top of a stack of five to six sieves which have successively smaller-sized openings from top to bottom. The stack is vibrated, and the particles eollect on top of the sieves. The data are usually represented in terms of percentage retained on the sieve, or percentage that is undersize or oversize vs. screen-opening size (Fig. 4) (6). 

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