Granulation

How to test if you need Granulation?

There are 3 reasons to granulate your formula.

1. To improve the flowability of your formulation.
2. To make your formulation more compressible.
3. To ensure a consistent spread of API throughout the formulation.

One way to test if your tablet formulation needs Granulation is to check your formulations flowability. A way to do this is to test the Angle of Incidence.

A small angle on the powder will show good flowability meaning its suitable for direct compression.

A high angle means your formulation may need granulation as it would not flow well and may potentially cause arching, bridging or rat holding within your tablet press.

Direct Compression

In tableting sometimes your tablets formulation needs neither dry granulation or wet granulation and can be directly compressed. This is the most cost-efficient process within tableting.

Your API and your excipients needed are taken and added to a mixer. Once blended they can be compressed in your tablet press with no further steps.

This is a great option for sensitive APIs that are maybe sensitive to both heat and moisture.

However, it needs to be mentioned that you should consider mix validation to ensure your tablet formulation has been mixed the correct amount and not too much. Please see our video on mix validation in the description below.

Granulation

Granulation is the process to produce larger granules, remove fines and to improve flowability within your formulation. There’s both wet granulation and dry granulation, before granulation you first have to complete your formulation including both API and excipients minus the lubrication.

Dry Granulation

Dry granulation is the combination of granules without the need of any liquid. Dry granulation is generally used if your formulation is sensitive to moisture or heat. Let’s look at slugging, which is using your tablet press to form large tablets that vary in weight due to the poor flowability of the formulation. The slugs created are then put through your granulator to be broken down into granules and then compressed once again for your final tablets.

Whilst reading about dry granulation you may have also heard of roller compaction. Roller compaction is where your formulation is fed through a roller compactor, your mix is fed through the top hopper where 2 rollers would compact the powder to form a ribbon, this would then pass through a granulator where the powder is forced against a mesh which creates the granules of the desired size. 

Wet Granulation

Whilst being one of the most complex forms of granulation, wet granulation is one of the most popular due to it being applicable to most formulations with the purpose to cause aggregation of particles.

The adhesive usually called a binder is incorporated in the form of a solution or suspension in a suitable liquid. The liquid should be non-toxic and is preferably water although other solvents are sometimes used.

The fluid bed granulator is one of the easiest forms of wet granulation as it all happens within the same unit. Hot air is fed into the bed lifting the granules whilst they are sprayed, the granules bind together to form bridges between themselves.

The initial phase of wet granulation is the spraying of the granules, the spray rate is dependant on your formulation. 

Next is the wetting of the powder begins to form liquid bridges between the granules.

The process is continued until the required size granule is formed with solid bridges between the granules.

Once complete your granules will go to the drying process, the spraying process is turned off and the hot air will continue to flow through the bed drying the granules.

There’s many different machines and processes for wet granulation such as:

Fluidized Bed Granulator

Planetary Mixer Granulator and

Rapid High Shear Granulator

After both wet and dry granulation, milling is needed to de-lump and create a standardized granule distribution. After milling, complete your final blend whilst adding lubricant, the lubricant is added after to coat the final granule which allows the formulation to flow easier through your press.

Whilst LFA doesn’t supply all of the equipment mentioned in this video, we do have a list of recommended suppliers that we would be happy to put you in contact with.