Sizing of Granulation

Few materials used in the manufacture of pharmaceutical dosage forms exist in the optimum size, and most materials must be reduced in size at some stage during production. The advantages of sizing of granules in tablet formulation development are as follows  

Mixing and blending of pharmaceutical ingredients are easier and more uniform if the ingredients are of approximately the same size and distribution. 

Improving color or active ingredient dispersion. Milling may reduce the tendency for mottling, and hence improve the uniformity of color from batch to batch. 

Wet milling produces uniformly sized wet granules, which promotes uniform and efficient drying. 

Improving imiformity of dosage units by virtue of uniformity of particle size distribution and reduction in the segregation of the mix. 

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The literature contains relatively little data on the physical properties of binder solutions and therefore conclusions must be drawn largely from qualitative observations. For example, Davies and Gloor (1972) have linked the effectiveness of binders with their adhesiveness or tackiness and have found that more viscous binder solutions increase the size of granules and reduce the bulk density. Hydroxypropylcedulose (HPG), with which atomising difficulties were encountered because of its viscosity, was responsible for the largest increase in mean particle... 

For oxidation of sulfur dioxide, measurements of effectiveness were made by Kadlec, Pour, and Regner [Coll. Czech. Chem. Commun. 33, 2388, 2526 (1968)] whose data are shown following. They are at atmospheric pressure. The initial content of SOz and the conversion have little effect on the result. Both increase in size of granule and temperature lower the effectiveness, although the effect of temperature is somewhat erratic. 

Eq. (18) is usually attributed to the variable-range hopping conductivity in presence of the Coulomb gap [34]. However, the analysis [72,75,76] shows that it is unrealistic explanation for the case of nanocomposites, because to fit experimental value on the basis of this theory one has to assume that the length of a single hop is less than the size of granules D and the electron... 

The size of granules shall lie within the following sieve limits (according to ISO 565) ... 

Rekhi GS Vuppala MK. Sizing of Granulation. In Parikh DM, ed. Handbook of Pharmaceutical Granulation Technology. New York Marcel Dekker, Inc., 1997 389. 

A computer model has been also developed to predict the porosity at the layer interface, as a function of the relative sizes of granules. From Table 12.1, it follows that measured and calculated resistances are comparable. This clearly proves the effect of infiltration on performance and shows that to increase the permeability of filtration elements new routes for synthesis limiting the extent of infiltrated zones are needed. 

Fig. 8.— Degree of Dextrinization at 160° of Starch, Depending on (a) Origin of Starch, (b) Size of Granules, and (c) Content of Amylose and Amylopectin. ...

The main difficulty arises in the adsorption of larger molecules that cannot successfully navigate the smaller pores to reach the internal surface, and thence they are adsorbed mainly on the external or boundary surface. Therefore, when large molecules such as colloids are to be adsorbed, it is desirable to use as small a size of granule as will give an adequate rate of flow of liquid. 

As told already, a copper powder is not formed of particles of identical size and morphology the individual particles may assume various forms and have very different surface areas for the same average size of granule [3]. As a result of this, it is not possible to relate the powder properties with the deposition process parameters and the deposition conditions, and, hence, a representative particle of the metal powder, having at least one property the same as the powder, should be determined. Obviously, a powder can then be considered as a group of identical particles. 

One practical approach during scale-up is to keep the processes dynamically similar, which is defined by the same dimensionless numbers for the two different sizes of granulators. Therefore, dimensionless numbers such as Froude number can be used for scale-up. 

Screening t Screening Optimizing the size of granules. Granule size affects the dissolution. 

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