It has been shown how the liquid requirements in wet granulation by mixergranulators are determined by the correlation between liquid saturation and mean granule size. The liquid required to achieve a reproducible granulation by a particular process is, however, dependent on a range of factors related to the feed material as well as the mixer and its operation influencing the densification of the agglomerates and, hence, the liquid saturation. Linkson etal. (1973) examined published data on wet granulation of insoluble materials, and found that granulation, in general, required 50-55% v/v liquid. This result is probably valid for low shear mixers such as rotating drums, while wet granulation in high shear mixers requires less liquid because of a more pronounced densification.
It might be expected that the amount of liquid required to agglomerate a powder should equal the amount required to saturate the agglomerates (Capes etal., 1977). This does not apply to all materials because moist agglomerates may become highly deformable at lower liquid saturations when particle interactions are weak, as demonstrated in experiments with lactose (Kristensen etal., 1984), and with glass spheres which agglomerate at liquid saturations below 10% because of the smooth surface of the spheres (Holm etal., 1985a).
It is likely that the use of relatively small amounts of granulating liquid, as applied in micro-granulation may suffice to remove the primary particles of the feed materials by nucleation. Das and Jarowski (1979) showed that micro-granulation leads to small granules with a relatively narrow size distribution. Moisture-activated dry granulation is a similar process which consists of an agglomeration stage that proceeds by the addition of small amounts of water to the dry solids containing a binder and, after agglomeration by agitation, the addition of a moisture-absorbing material, e.g. microcrystalline cellulose (Ullah etal., 1987; Chen etal., 1990). The resulting product is a dry granulation.
Early work has shown that the liquid requirements are strongly dependent on feed material properties and the type of mixer-granulator (Ganderton and Hunter, 1971; Hunter and Ganderton, 1972, 1973). With high shear mixers in particular, it is difficult to predict the liquid requirements within the narrow limits required to control and reproduce the process. For production purposes, the only practical approach is to employ instrumentation capable of detecting the phases of the process and, thus, the proper amount of binder liquid and the appropriate wet massing time (the granulation endpoint) to produce a granulation with the desired quality (size distribution, density, friability etc).
In fluidized bed granulation, granule growth is determined primarily by the moisture content of the bed and the droplet size of the atomized binder solution. The process proceeds by simultaneous liquid addition and solvent evaporation. If the moisture content is too high, the bed becomes overwetted and defluidizes rapidly. If the moisture content is too low, no agglomeration occurs. The liquid requirements are, therefore, determined primarily by the process conditions, especially by the liquid addition rate and the temperature and flow rate of the fluidizing air. The humidity of the air affects, to some extent, the moisture content of the bed.
A basic instrumentation for fluidized bed granulation must include the parameters determining the moisture content of the bed and the atomiza-tion of the binder solution, i.e. the inlet air temperature and humidity, inlet air-flow rate, liquid flow rate, and the pressure and flow rate of the atomizing air (Aulton and Banks, 1981; Kristensen and Schaefer, 1987).
Fig. 19 Effect of moisture content on granule size (a) and intragranular porosity (b) in granulation of calcium hydrogen phosphate in two different mixer-granulators. Fielder PMAT 25: feed 7 kg, liquid addition rate 100 g min impeller speed 500 r.p.m. (■) and 250 r.p.m. (□). Lodige M5G: feed 1.5 kg, liquid addition rate 25 g min impeller speed 250 r.p.m. (▲) and 100 r.p.m. (A). Adapted from Schaefer et a/.
(1986a) with permission from the authors.
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