Production statistics granule

Granulation and discoloration of kidneys and a decrease in kidney-to-brain-weight ratio was reported in minks fed 6.19 mg/kg/day of heptachlor daily for 28 days (Aulerich et al. 1990). Rats receiving 0.5 mg/kg/day of heptachlor in the diet in an intermediate-duration study showed a statistically significant increase in blood urea (Enan et al. 1982). Increased blood urea may indicate renal inefficiency in metabolism and clearance of protein by-products. This study is limited in that histologic examination was not included in the study design and insufficient dose levels were utilized to establish a dose response. 

Pore diameters and their distribution. Small pores limit accessibility of internal surface because of increased resistance to diffusion of reactants inwards. Diffusion of products outward also is slowed down and may result in degradation of those products. When the catalyst is expensive, the inaccessible internal surface is a liability. A more or less uniform pore diameter is desirable, but the distribution usually is statistical and only molecular sieves have nearly uniform pores. Those catalyst granules that are extrudates of compacted masses of smaller particles have tamodal pore size distribution, between the particles and within them. Clearly a compromise between large specific surface and its accessibility as measured by pore diameter is required in some situations. 

Empirical correlations can be as simple as a curvilinear plot between the average granulation liquid requirements between machines in development and production, for a variety of products. More advanced correlations employ a statistical attempt to map the effects of the high-shear granulation parameters for various machines and machine sizes. 

P. Wehrl, G. F. Palmieri, and A. Stamm, The Taguchi s performance statistic to optimize theophylline beads production in a high speed granulator, Dmg Dev. Ind. Pharm., 20, 2823-2843 (1994). 

During product development, it is prudent to systematically evaluate the effect of MBP particulate properties on the properties of granules, tablet compaction, and dissolution preferably based on a statistically controlled experimental protocol to discern the interplay of the relevant interactions (Fig. 12.8). Due to the high polymeric content, the primary mode of compaction with amorphous materials is plastic deformation and as such the final compaction is sensitive to the dry granulation conditions (Herting and Kleinebudde 2008). 

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