Granulation is the process in which primary powder particles are made to adhere to form larger, multiparticle entities called granules. Pharmaceutical granules typically have a size range between 0.2 and 4.0 mm, depending on their subsequent use.

Granulation normally commences after initial dry mixing of the necessary powdered ingredients so that a uniform distribution of each ingredient through the mix is achieved. After granulation the granules will either be packed (when used as a dosage form e.g effervescent granule, soluble granule), or they may be mixed with other excipients prior to tablet compaction or capsule filling.

Why Granulation ?

The reasons why granulation is often necessary are as follows.
1. To prevent segregation of the constituents of the powder mix
2. To improve the flow properties/fluidity of the mix
3. To improve the compaction characteristics of the mix
4. Other reasons


To prevent segregation of the constituents of the powder mix
Segregation (demixing) is because there are differences in the size or density of the components of the mix, the smaller and/or denser particles concentrating at the base of a container while the larger and/or less dense ones above them (on the top). An ideal granulation will contain all the constituents of the mix in the correct proportion in each granule, and segregation of the ingredients will not occur.

Particle size distribution of the granules is important because, if there is a wide size distribution, the granules themselves may segregate although the individual components may not segregate. If this occurs in the hoppers of sachet filling machines, capsule-filling machines or tablet machines, products with large weight variations will result. This is because these machines fill by volume rather than weight, and if different regions in the hopper contain granules of different sizes (and hence bulk density), a given volume in each region will contain a different weight of granules. This will lead to an unacceptable distribution of the drug content within the batch of finished product, even though the drug is evenly distributed, weight per weight, through the granules.



To improve the flow properties/fluidity of the mix
Flow property/Fluidity is required to produce tablets of a consistent weight and uniform
strength. Many powders not flowing well because they had small size, irregular shape or surface characteristics. Poor flow will often result in a wide weight variation within the final product owing to variable fill of tablet dies etc. Granules produced from such a cohesive system will be larger and more isodiametric, both factors contributing to improved flow properties.

To improve the compaction characteristics of the mix
Compressibility is required to form a stable, intact compact mass when pressure is
applied. Some powders are difficult to compact even if a readily compactable adhesive is included in the mix, but granules of the same formulation are often more easily compacted and produce stronger tablets. This is associated with the distribution of the adhesive within the granule and is a function of the method employed to produce the granule. Often solute migration occurring during the post-granulation drying stage results in a binder-rich outer layer to the granules. This in turn leads to direct binder–binder bonding, which assists the consolidation of weakly bonding materials.

Other reasons
The above are the primary reasons for the granulation of pharmaceutical/consumer good products, but there are other reasons that may necessitate the granulation of powdered material:
  1. Avoid dustiness. The granulation of toxic materials will reduce the hazard associated with the generation of toxic dust that may arise when handling powders. Thus granules should be non-friable and have a suitable mechanical strength.
  2. Materials which are slightly hygroscopic may adhere and form a cake if stored as a powder. Granulation may reduce this hazard, as the granules will be able to absorb some moisture and yet retain their flowability because of their size.
  3. Granules, being denser than the parent powder mix, occupy less volume per unit weight. They are therefore more convenient for storage or shipment.
  4. mprove appearance, mixing properties in general to either eliminate undesirable properties or to improve the physical and chemical properties of fine powders.

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