Granulation and Particle-Bonding Mechanism of Granulation : Pharmaceutical Guidelines

Granulation and Particle-Bonding Mechanism of Granulation

All about Granulation including Reasons for granulation, Bonding mechanisms between particles, Mechanisms of granule formation and methods for granulation.

What is Granulation?

Granulation is the process in which powder particles are made to adhere to form agglomerates called granules.

Why Granulation?

To prevent segregation of the constituents of the mix.
lTo improve the flow properties of the mix.
lTo change the particle size distribution so as to improve the compressibility and to increase apparent density of the powder.

Reasons for granulation are:

lGranulation of toxic material reduce the hazard associated with handling of toxic dust. Granulation should be non-friable & have suitable mechanical strength.
lFor slightly hygroscopic material granulation reduces possibility of caking. As granules can absorb more moisture yet retain their flow ability because of their size.
lGranules being compact than the powder occupy lesser volume per unit weight therefore they are more convenient for storage and shipment.

Bonding mechanisms between particles:

1. Adhesion and cohesion forces in the immobile liquid films between individual primary powder particles.
2. Interfacial forces in mobile liquid films within the granules;    
3. The formation of solid bridges after solvent evaporation;
4. Attractive forces between solid particles;
5. Mechanical interlocking.
6. Granulation can improve or modify drug release profile.

Mechanisms of granule formation:

In the dry granulation methods, particle adhesion takes place because of compaction forces. A compact or sheet is produced which is larger than the granule size required, and therefore the required size can attained by milling and sieving.
In subsequent wet granulation methods, binder added to dry powders has to be distributed through out  the powder by  the mechanical agitation created in the granulator. The particles adhere to each other because of binder, and further kneading causes more particles to adhere. The precise mechanism by which a dry powder is transformed into a bed of granules varies for each type of granulation.
Nucleation: Granulation starts with particle to particle contact and adhesion due to liquid bridges. Number of particles will join to form the pendular state.
Transition: Nuclei can grow in two possible ways either single particles can be added to the nuclei by pendular bridges, or two or more nuclei may combine. The combined nuclei will be reshaped by the agitation of the bed.
Ball growth: Granule growth produces large, spherical granules and the mean particle size of the granulating system will increase with time and agitation.
Chopping: Bigger size are granules are chopped to smaller granules in the process of ball growth. Chopping is repeated to achieve the granulation end point.
Granulation and Particle-Bonding Mechanism of Granulation
Particle-Bonding Mechanism

There are two methods for granulation:
1.Wet granulation method:  In this granulation binder solution is used.
2.Dry Granulation:  Granulation is achieved with the help of mechanical compaction or force.

Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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